Key points
Each chapter's “most frequently asked” box and its closing “key points for the board”, in one place for the final review.
1. Atomic and Nuclear Physics
Thomson → discovered the electron (cathode rays, 1897)
Rutherford → discovered the nucleus (alpha scattering experiment, 1911)
Bohr → quantised energy levels (1913), ΔE = hν
Quantum mechanical model → probability clouds (orbitals), 4 quantum numbers, Pauli exclusion principle
Isotope → same Z (protons), different N → Example: I-123, I-125, I-131
Isobar → same A (mass), different Z → Example: Mo-99, Tc-99
Isotone → same N (neutrons), different Z
Thomson → discovered the electron (cathode rays, 1897)
Rutherford → discovered the nucleus (alpha scattering experiment, 1911)
Bohr → quantised energy levels (1913), ΔE = hν
Quantum mechanical model → probability clouds (orbitals), 4 quantum numbers, Pauli exclusion principle
Isotope → same Z (protons), different N → Example: I-123, I-125, I-131
Isobar → same A (mass), different Z → Example: Mo-99, Tc-99
Isotone → same N (neutrons), different Z
Isomer → same Z and A, different energy state → Example: Tc-99m / Tc-99
1 amu = 931.5 MeV
Electron/positron mass = 0.511 MeV
Annihilation photon energy = 511 keV (each)
β⁺ decay threshold = 1.022 MeV
Tc-99m gamma energy = 140 keV
I-131 gamma energy = 364 keV
Strong nuclear force → holds the nucleus together
Weak nuclear force → responsible for beta decay
Electromagnetic force → repulsion between protons (Coulomb)
Gravitational force → negligible on the nuclear scale
Magic numbers: 2, 8, 20, 28, 50, 82, 126
Example of a doubly magic nucleus: Pb-208 (Z=82, N=126)
Even–even nuclei are the most stable, odd–odd the least stable
Only 4 stable odd–odd nuclei in nature: ²H, ⁶Li, ¹⁰B, ¹⁴N
Fe-56 → highest BE/A → most stable nucleus
Neutron excess → β⁻ decay (e.g. I-131, Mo-99)
Proton excess → β⁺ or EC (e.g. F-18 → β⁺, Tl-201 → EC, Ga-67 → EC)
Heavy nucleus (Z > 83) → α decay (e.g. Ra-223, Ra-226)
Excited nucleus → isomeric transition/internal conversion (e.g. Tc-99m → IT)
Low Z → Auger electron dominates
High Z → characteristic X-ray dominates
Kα X-ray = E_K − E_L; KLL Auger electron ≈ E_K − 2E_L
I-125 → Auger emitter → high-LET-like effect when close to DNA
U-238 → Pb-206
U-235 → Pb-207
Th-232 → Pb-208 (doubly magic)
Maximum electrons = 2n²
K=2, L=8, M=18, N=32
2. Radioactive Decay
Neutron excess → β⁻ decay → Z increases by 1, A unchanged
Proton excess → β⁺ or EC → Z decreases by 1, A unchanged
Heavy nucleus (Z > 83) → α decay → Z decreases by 2, A decreases by 4
Excited nucleus → isomeric transition (IT) → Z and A unchanged
β⁺ threshold: 1.022 MeV → below the threshold only EC occurs
β⁻: n → p + e⁻ + ν̄ₑ → Z increases → an antineutrino is emitted
β⁺: p → n + e⁺ + νₑ → Z decreases → a neutrino is emitted → threshold: 1.022 MeV
Neutron excess → β⁻ decay → Z increases by 1, A unchanged
Proton excess → β⁺ or EC → Z decreases by 1, A unchanged
Heavy nucleus (Z > 83) → α decay → Z decreases by 2, A decreases by 4
Excited nucleus → isomeric transition (IT) → Z and A unchanged
β⁺ threshold: 1.022 MeV → below the threshold only EC occurs
β⁻: n → p + e⁻ + ν̄ₑ → Z increases → an antineutrino is emitted
β⁺: p → n + e⁺ + νₑ → Z decreases → a neutrino is emitted → threshold: 1.022 MeV
EC: p + e⁻ → n + νₑ → Z decreases → a neutrino is emitted → no threshold
β⁻ and β⁺: continuous energy spectrum
EC: monoenergetic neutrino + characteristic X-ray/Auger
Monoenergetic: alpha particles, internal conversion electrons, gamma rays, Auger electrons, characteristic X-rays
Continuous spectrum: beta particles (β⁻ and β⁺), bremsstrahlung X-rays
Y-90 (Emax = 2.28 MeV, T½ = 64.1 h)
P-32 (Emax = 1.71 MeV, T½ = 14.3 days)
Sr-89 (Emax = 1.46 MeV, T½ = 50.5 days)
Sr-90 (Emax = 0.546 MeV, T½ = 28.8 years)
Pure beta emitters cannot be imaged directly → bremsstrahlung SPECT; for Y-90 also PET via internal pair production
Rb-82: 75 seconds (shortest, cardiac PET)
O-15: 2.04 minutes
N-13: 10 minutes
C-11: 20.4 minutes
Ga-68: 68 minutes
F-18: 110 minutes
Tc-99m: 6.01 h
I-123: 13.2 h
Mo-99: 66 h
Y-90: 64.1 h
In-111: 67.3 h
Tl-201: 73 h
Ga-67: 78.3 h
Lu-177: 6.65 days
I-131: 8.02 days
Ra-223: 11.4 days
P-32: 14.3 days
Cr-51: 27.7 days
Sr-89: 50.5 days
I-125: 59.4 days
Co-57: 271.8 days
Ge-68: 271 days
Co-60: 5.27 years
A = λN = (0.693/T½) × N
A(t) = A₀ × e−λt = A₀ × (1/2)t/T½
1 Ci = 3.7 × 10¹⁰ dps = 37 GBq
1 mCi = 37 MBq
1 µCi = 37 kBq
Mean beta energy = Emax/3
Te = (Tp × Tb) / (Tp + Tb)
Te is always shorter than both Tp and Tb
The shorter half-life determines the effective half-life more
τ = 1/λ = 1.443 × T½
τ is always longer than T½
Cumulated activity: Ã = A₀ × τ = 1.443 × A₀ × T½
Transient equilibrium: T½(parent) > T½(daughter), same order → A(daughter) > A(parent) → Example: Mo-99/Tc-99m
Secular equilibrium: T½(parent) >> T½(daughter) → A(daughter) = A(parent) → Example: Sr-82/Rb-82, Ge-68/Ga-68
No equilibrium: T½(daughter) > T½(parent) → no equilibrium is established
Other examples of secular equilibrium: Ra-226/Rn-222 (classic example in nature) and the Rb-81/Kr-81m generator
Transient equilibrium
At equilibrium the Tc-99m/Mo-99 ratio is theoretically 1.1; with 87.5% branching actually ≈0.96
tmax ≈ 23 h
At tmax ideally A(daughter) = A(parent); for Mo/Tc A(Tc) ≈ 0.88 × A(Mo)
At equilibrium Tc-99m decreases with the half-life of Mo-99 (66 h)
Daily elution (~24 h) is close to tmax → optimal yield
F-18 < C-11 < N-13 < O-15 ≈ Ga-68 < Rb-82
Short range → good resolution
F-18: best resolution
Rb-82: poorest resolution
Arrow down to the right → β⁻ (Z increases)
Arrow down to the left → β⁺ or EC (Z decreases)
Vertical arrow down → IT or gamma (Z unchanged)
Top line → parent nucleus
Bottom line → daughter ground state
Intermediate lines → excited states
High Z
Low transition energy
Large change in angular momentum (ΔL)
IC and Auger electrons are absorbed locally in tissue → no contribution to imaging, they only increase the patient dose
F-18: 96.7% β⁺ + 3.3% EC
Cu-64: 17.6% β⁺ + 38.5% β⁻ + 43.9% EC (a rare radionuclide with both β⁺ and β⁻ decay)
Tc-99m: ~100% IT → of which 88.5% is 140 keV gamma emission + 11.5% internal conversion (IC)
Activity (Bq) = decay rate ≠ photon emission rate → number of photons = activity × gamma yield
1 MBq Tc-99m → ~0.89 × 10⁶ 140 keV photons/s
Positron + electron → short-lived positronium → annihilation → 2 × 511 keV (~180°)
3. Interaction of Radiation with Matter
Alpha: Heavy (4 amu), +2e charge, straight path, short range (~50 µm in tissue), high LET (~80 keV/µm), has a Bragg peak, shielding: paper/skin is enough
Beta: Light (0.000549 amu ≈ 1/1836 of the proton mass), ±1e charge, tortuous path, longer range (a few mm in tissue), low LET (~0.2 keV/µm), no Bragg peak, shielding: Perspex (low Z)
Photon: Massless, uncharged, exponential attenuation, no concept of range (HVL is used), low LET, shielding: lead (high Z)
Bremsstrahlung ∝ Z × E (high Z and high energy → more bremsstrahlung)
Beta shielding → low Z (Perspex) → bremsstrahlung minimised
Gamma shielding → high Z (lead) → photoelectric absorption maximised
Two-layer shielding (for pure beta emitters): inner = Perspex (stops beta) + outer = lead (shields bremsstrahlung)
Alpha: Heavy (4 amu), +2e charge, straight path, short range (~50 µm in tissue), high LET (~80 keV/µm), has a Bragg peak, shielding: paper/skin is enough
Beta: Light (0.000549 amu ≈ 1/1836 of the proton mass), ±1e charge, tortuous path, longer range (a few mm in tissue), low LET (~0.2 keV/µm), no Bragg peak, shielding: Perspex (low Z)
Photon: Massless, uncharged, exponential attenuation, no concept of range (HVL is used), low LET, shielding: lead (high Z)
Bremsstrahlung ∝ Z × E (high Z and high energy → more bremsstrahlung)
Beta shielding → low Z (Perspex) → bremsstrahlung minimised
Gamma shielding → high Z (lead) → photoelectric absorption maximised
Two-layer shielding (for pure beta emitters): inner = Perspex (stops beta) + outer = lead (shields bremsstrahlung)
Pure beta emitters: Y-90, P-32, Sr-89 → Perspex shield essential
Photoelectric: ∝ Z³/E³ → dominant at high Z, low E → photon completely absorbed → NO scattered photon
Compton: independent of Z, depends on density → dominant at intermediate E → photon partly absorbed → scattered photon PRESENT
Pair production: ∝ Z² → threshold: 1.022 MeV → dominant at high E, high Z → e⁻/e⁺ pair is created
Coherent: low E, high Z → NO energy transfer → direction changes
Soft tissue (Z ≈ 7.4): ~30 keV → Compton → ~20 MeV
Bone (Z ≈ 14): ~50 keV → Compton → ~15 MeV
Lead (Z = 82): ~500 keV → Compton → ~5 MeV
Board rule: at nuclear medicine energies (70-511 keV) Compton ALWAYS dominates in soft tissue
Iodine (I, Z=53): 33.2 keV
Barium (Ba, Z=56): 37.4 keV
Tungsten (W, Z=74): 69.5 keV
Lead (Pb, Z=82): 88 keV
Above the K-edge the probability of the photoelectric effect rises abruptly
Compton formula: E′ = E / [1 + (E/511)(1 − cos θ)]
180° backscatter: E′ = E / [1 + 2E/511]
140 keV → 180° backscatter → ~91 keV (scattered photon), ~49 keV (Compton electron)
511 keV → 180° backscatter → ~170 keV (scattered photon), ~341 keV (Compton electron)
θ = 0° → no energy transfer (E' = E)
θ = 180° → maximum energy transfer
Tc-99m (140 keV): 0.3 mm Pb
Tl-201 (69-83 keV X-rays): 0.2 mm Pb
I-131 (364 keV): 3 mm Pb
F-18 (511 keV): 4 mm Pb
Cs-137 (662 keV): 6.5 mm Pb
Co-60 (1.25 MeV): 12 mm Pb
Rule: HVL increases with energy (thicker shielding needed)
HVL = 0.693 / µ = ln2 / µ
TVL = 2.303 / µ = ln10 / µ
TVL = 3.32 × HVL
Fraction transmitted after n HVL = (1/2)ⁿ
1 HVL → 50%, 2 HVL → 25%, 3 HVL → 12.5%, 4 HVL → 6.25%, 5 HVL → 3.125%
Formula: I₁ × d₁² = I₂ × d₂²
Distance 2× → dose 1/4
Distance 3× → dose 1/9
Distance 4× → dose 1/16
Distance 10× → dose 1/100
Valid only for point sources
Line source: 1/d, plane source: ~constant at close range
Tl-201 (0.45) < Ga-67 (0.76) < Tc-99m (0.78) < I-131 (2.17) < In-111 (3.21) < Cs-137 (3.26) < F-18 (5.73) < Ra-226 (8.25) < Co-60 (13.2)
Formula: Ḋ = Γ × A / d²
Higher Γ → higher dose for the same activity → more protection needed
PET radiopharmaceuticals (F-18) have a higher Γ than SPECT agents (Tc-99m) → staff dose is higher in PET
Time: Reduce the time → D = Ḋ × t
Distance: Move away → inverse square law (most effective and cheapest method)
Shielding: Choose a suitable material (gamma → Pb, beta → Perspex, alpha → prevent contamination, neutron → hydrogen-rich material)
Activity: Use the lowest diagnostic dose
Training: Train the staff
W value: Average energy needed to create one ion pair = ~34 eV (in air, approximately the same for all types of radiation)
LET: Energy transferred to the medium per unit path length (keV/µm) → varies with the type of radiation
Specific ionisation: Number of ion pairs per unit path length → alpha >> beta
The W value is constant; LET and specific ionisation depend on the type of radiation
Stopping power ∝ z²/v² (Bethe–Bloch) → with the same mass and velocity, a 2-fold charge reduces the range to ~1/4
Delta (δ) rays: secondary electrons ejected by the primary charged particle that can themselves cause ionisation
Narrow beam: B = 1 (scattered photons do not reach the detector)
Broad beam: B > 1 (scattered photons also contribute)
B increases with material thickness
B must be taken into account in radiation protection calculations → otherwise shielding will be inadequate
X-ray spectrum: continuous part → bremsstrahlung; sharp peaks → characteristic X-rays
Maximum photon energy = tube voltage (120 kV → 120 keV)
Total number of photons ∝ mA × kV²
Difference between X-ray and gamma → origin (outside the nucleus vs nucleus), not energy
Ionisation threshold: 13.6 eV; EURATOM: ≤100 nm (≥3 × 10¹⁵ Hz)
Imaging windows: X-ray (CT, SPECT, PET), radiofrequency (MR), ultrasound (US)
511 keV photons in soft tissue: >95% Compton
4. Radiobiology
Direct action: Radiation → direct DNA damage → dominant at high LET → independent of oxygen
Indirect action: Radiation → radiolysis of water → OH• radical → DNA damage → dominant at low LET (~ 70%) → oxygen-dependent
Most important free radical: OH• (hydroxyl radical)
Oxygen fixation hypothesis: O₂ makes free radical damage permanent
Base damage: Most frequent, most easily repaired, usually not lethal
SSB: Frequent (~1000/Gy), easily repaired (opposite strand as template), usually not lethal
DSB: Rare (~40/Gy), difficult to repair, the MOST IMPORTANT cause of cell death
Direct action: Radiation → direct DNA damage → dominant at high LET → independent of oxygen
Indirect action: Radiation → radiolysis of water → OH• radical → DNA damage → dominant at low LET (~70%) → oxygen-dependent
Most important free radical: OH• (hydroxyl radical)
Oxygen fixation hypothesis: O₂ makes free radical damage permanent
Base damage: Most frequent, most easily repaired, usually not lethal
SSB: Frequent (~1000/Gy), easily repaired (opposite strand as template), usually not lethal
DSB: Rare (~40/Gy), difficult to repair, the MOST IMPORTANT cause of cell death
Clustered damage: Characteristic of high LET, very difficult to repair, most lethal
BER: Single-base damage → fast, efficient
NER: Bulky lesions (UV damage) → defective in xeroderma pigmentosum
HR: DSB repair → error-free → only in S/G2 phase → BRCA1/2 required
NHEJ: DSB repair → error-prone → active in all phases → the dominant DSB repair pathway in mammalian cells
MMR: Replication errors → defective in Lynch syndrome
Mitotic death: The most frequent type of radiation-induced death → death during division
Apoptosis: Programmed death → p53-mediated → dominant in lymphocytes (interphase death)
Necrosis: Disordered death → at very high doses
Senescence: Permanent arrest of division → the cell is alive but does not divide
SF = e−(αD + βD²)
α/β ratio = the dose at which the linear and quadratic components are equal
High α/β (~10 Gy): Early-responding tissue, tumours → little shoulder → little affected by fractionation
Low α/β (~2-3 Gy): Late-responding tissue → marked shoulder → strongly affected by fractionation
Exception: Prostate cancer has a low α/β (~1.5-3 Gy) → behaves like a late-responding tissue
Most sensitive: M phase and late G2
Most resistant: Late S phase (HR active, repair enzymes high)
Intermediate: G1 phase
G0: Usually radioresistant (non-dividing cells)
Most sensitive → Most resistant: Lymphocyte > Spermatogonia > Erythroblast > Intestinal crypt > Basal epidermis > Endothelium >
Exception to Bergonié-Tribondeau: Lymphocytes are very radiosensitive despite high differentiation (apoptosis) LET – RBE – OER Relationship (Golden Triangle)
LET↑ → RBE↑ (up to 100 keV/µm, then overkill → RBE↓)
LET↑ → OER↓ (the oxygen effect disappears at high LET)
Optimal LET: ~100 keV/µm → maximum RBE
Low LET (gamma, X-ray): RBE = 1, OER ≈ 2.5-3.0, indirect action dominant
High LET (alpha): RBE ≈ 20, OER ≈ 1.0, direct action dominant
X-ray / Gamma: RBE = 1 (reference)
Beta: RBE ≈ 1
Proton: RBE ≈ 1.1
Thermal neutron: RBE ≈ 2-5
Fast neutron: RBE ≈ 10-20
Alpha: RBE ≈ 20
RBE formula: RBE = reference dose / test dose (for the same biological effect)
Deterministic: Threshold PRESENT → severity increases with dose → cell death → early or late (e.g. cataract, fibrosis) effect → predictable → Examples: cataract, epilation, sterility, erythema, radiation syndromes
Stochastic: NO threshold (LNT) → probability increases with dose (not severity) → cell mutation → late effect → unpredictable at the individual level → Examples: cancer, hereditary effects
Cataract threshold: ~0.5 Gy (ICRP 118 update – this value is asked in the exam!)
Radiation-associated leukaemias: AML, CML, ALL → CLL is NOT radiation-associated
Radiation does not create new types of mutation; it increases the frequency of spontaneous mutations (most are recessive)
LNT: Standard for stochastic effects → accepted by the ICRP → basis of radiation protection regulations
Threshold model: Applies to deterministic effects
Hormesis: Protective effect at low dose → controversial → not used in regulations
BEIR VII (atomic bomb data): leukaemia risk linear-quadratic, solid cancer risk linear
Haematopoietic syndrome: 1-8 Gy → bone marrow → pancytopenia → LD₅₀/₆₀ ≈ 3.5-4.5 Gy (untreated)
GI syndrome: 8-30 Gy → intestinal crypt → bloody diarrhoea, sepsis → death at ~10-14 days
Neurovascular syndrome: >30 Gy → CNS → convulsions, coma → death within 24-72 hours → no treatment
Four clinical phases: Prodromal → Latent → Manifest illness → Recovery/Death
Early onset of prodromal symptoms = indicator of high dose
1. Lymphocyte (hours-days) → FASTEST → biological dosimeter 2. Neutrophil (2-3 weeks) 3. Platelet (3-4 weeks) 4. Erythrocyte (last – lifespan ~120 days) → SLOWEST
1. Repair: Sublethal damage repair → spares late-responding tissues 2. Reassortment (Redistribution): Transition from the resistant S phase to the sensitive G2/M → against the tumour 3. Repopulation: Surviving cells multiply → in favour of normal tissue, against tumour control (tumour cells also multiply; becomes marked as treatment time lengthens)
4. Reoxygenation: Hypoxic cells become oxygenated → radiosensitivity increases → against the tumour
– 5th R: Radiosensitivity (intrinsic radiosensitivity)
Preimplantation (0-9 days): "All or none" → death or normal development
Organogenesis (2-8 weeks): HIGHEST risk of congenital anomalies → teratogenic period
Early fetal (8-15 weeks): HIGHEST risk of mental retardation → period of neuronal migration → ~25-30 IQ points/Gy lost
Late fetal (16-25 weeks): Lower risk of mental retardation → ~10-13 IQ points/Gy lost
>25 weeks: Very low risk of marked anomalies/mental retardation → childhood cancer risk (stochastic)
<50 mGy: NO INDICATION for therapeutic abortion
I-131 therapy is ABSOLUTELY CONTRAINDICATED in pregnancy (the fetal thyroid concentrates iodine after weeks 10-12)
Amifostine (WR-2721): The most important clinical radioprotector → free radical scavenger → selectively protects normal tissue → FDA approved (prevention of xerostomia)
Amifostine does not cross the blood-brain barrier → does not protect the CNS; most marked protection in the salivary glands and kidney
Oxygen: The most potent natural radiosensitiser
Hypoxic cell sensitisers: Misonidazole, nimorazole → mimic oxygen
Halogenated pyrimidines: BrdU, IdU → incorporated into DNA → effective only in the S phase
D₀: Dose that reduces survival to 37% → low D₀ = high radiosensitivity
Dq: Shoulder width → large Dq = good repair capacity
n: Extrapolation number → if n = 1 there is no shoulder (high LET)
High LET: No shoulder, curve steep from the start, n ≈ 1
Low LET: Marked shoulder, the curve starts shallow then steepens
SLDR (sublethal damage repair): Repair between two fractions (~6 hours) → Elkind recovery → marked at low LET
PLDR (potentially lethal damage repair): Repair possible if division is delayed → marked in slow-growing tumours → a cause of radioresistance
Low dose rate → time for repair → survival increases → biological effect decreases
High dose rate → insufficient repair → damage accumulates → biological effect increases
Inverse dose-rate effect: At low dose rate cells accumulate in G2/M → paradoxically more death (in some tumour lines)
1. Physical stage: ~10⁻¹⁸ – 10⁻¹² seconds → ionisation/excitation → SHORTEST 2. Chemical stage: ~10⁻¹² – 10⁻² seconds → free radical formation 3. Biological stage: Seconds – years → DNA repair, cell death, cancer → LONGEST
Adaptive response → 1-100 mGy priming dose followed by protection
Bystander → response in a non-irradiated neighbouring cell; Abscopal → immune-mediated response in a distant metastasis (DAMP)
ICRP 103 nominal risk: cancer ~5.5%/Sv, heritable ~0.2%/Sv
<100 mGy → no clinically relevant functional impairment expected in any tissue
Optimal LET ~100 keV/µm → ionisation spacing = DNA diameter; Auger electrons in the high-LET group; TAT ~100 keV/µm
BED = n·d·[1 + d/(α/β)] → comparison of radionuclide therapies
Intrinsic apoptosis → cytochrome c/Apaf-1/caspase 9; extrinsic → caspase 8
Hypoxia → HIF-1α → VEGF (VEGFR-2); Warburg effect → FDG uptake
Somatostatin receptor = GPCR; PD-1 (T cell) – PD-L1 (tumour)
"Most important free radical?" → OH• (hydroxyl radical)
"Most important cause of cell death?" → DSB (double-strand break)
"Most radiosensitive somatic cell?" → Lymphocyte
"Most radioresistant somatic cell?" → Nerve cell (neuron)
"Most radiosensitive cell cycle phase?" → M phase (and late G2)
"Most radioresistant cell cycle phase?" → Late S phase
"Most frequent type of radiation-induced cell death?" → Mitotic death
"Type of death in lymphocytes?" → Apoptosis (interphase death)
"Radiation protection model?" → LNT (Linear No-Threshold Model)
"Clinical radioprotector?" → Amifostine (WR-2721)
"Most potent natural radiosensitiser?" → Oxygen
"LD₅₀/₆₀ (untreated)?" → ~3.5-4.5 Gy
"First cell to fall in ARS?" → Lymphocyte
"Last cell to fall in ARS?" → Erythrocyte
"Most sensitive period for mental retardation?" → 8-15 weeks (early fetal)
"Most sensitive period for congenital anomalies?" → 2-8 weeks (organogenesis)
"Effect of radiation in preimplantation?" → All or none
"Dose in pregnancy not requiring abortion?" → <50 mGy
"DSB repair mechanism active in all phases?" → NHEJ
"Error-free DSB repair mechanism?" → HR (only S/G2)
"Cataract threshold dose (ICRP 118)?" → ~0.5 Gy
"Exception to Bergonié-Tribondeau?" → Lymphocyte (radiosensitive despite high differentiation)
5. Radiation Detection Systems
Ionisation chamber: NO gas amplification → current mode → energy-independent → dose calibrator, survey meter, pocket dosimeter
Proportional counter: Gas amplification PRESENT (10³-10⁶) → pulse mode → CAN discriminate energy → alpha-beta discrimination, neutron detection
GM counter: Maximum amplification (10⁸-10¹⁰) → pulse mode → CANNOT discriminate energy → most sensitive → longest dead time (~100-300 µs) → contamination survey
Recombination → Ionisation → Proportional → Limited proportional → Geiger-Müller → Continuous discharge
NaI(Tl): Gamma camera standard → highest light output among classical scintillators → energy resolution ~10% → hygroscopic → 3/8-inch thickness (for Tc-99m)
BGO: Older PET crystal → highest effective Z → best stopping power → BUT slow (300 ns) → CANNOT do TOF → low light output
LSO/LYSO: Modern PET standard → fast (~40 ns) → TOF-PET possible → high light output → Lu-176 background activity
Ionisation chamber: NO gas amplification → current mode → energy-independent → dose calibrator, survey meter, pocket dosimeter
Proportional counter: Gas amplification PRESENT (10³-10⁶) → pulse mode → CAN discriminate energy → alpha-beta discrimination, neutron detection
GM counter: Maximum amplification (10⁸-10¹⁰) → pulse mode → CANNOT discriminate energy → most sensitive → longest dead time (~100-300 µs) → contamination survey
Recombination → Ionisation → Proportional → Limited proportional → Geiger-Müller → Continuous discharge
NaI(Tl): Gamma camera standard → highest light output among classical scintillators → energy resolution ~10% → hygroscopic → 3/8-inch thickness (for Tc-99m)
BGO: Older PET crystal → highest effective Z → best stopping power → BUT slow (300 ns) → CANNOT do TOF → low light output
LSO/LYSO: Modern PET standard → fast (~40 ns) → TOF-PET possible → high light output → Lu-176 background activity
CZT: Semiconductor → best energy resolution (in clinical use) → direct conversion → no PMT needed → compact → expensive
HPGe: Absolutely the best energy resolution → BUT cooling needed (77 K) → no clinical use
PMT: High gain (10⁶-10⁷) → SENSITIVE to magnetic fields → cannot be used in PET/MR → large size → high voltage (~1000-2000 V)
SiPM: High gain (10⁶) → INSENSITIVE to magnetic fields → used in PET/MR → compact → low voltage (~30-70 V) → dark current (noise) → temperature-sensitive
Dose calibrator → Radiopharmaceutical activity measurement (µCi-mCi)
Well counter → In vitro sample activity measurement (nCi-pCi)
GM counter → Contamination survey
Gamma probe → Intraoperative sentinel lymph node localisation
Thyroid uptake probe → Measurement of thyroid iodine uptake
LSC (liquid scintillation counter) → H-3, C-14 (low-energy beta emitters)
Proportional counter → Alpha-beta discrimination, neutron detection
Detection efficiency = geometric efficiency × intrinsic efficiency; increasing the distance lowers only the geometric efficiency
Well counter: dead-time loss at >~1 µCi; geometric efficiency falls as sample volume increases → standard and sample are counted in the same volume/tube
RIA (competitive): count INVERSELY proportional to antigen; IRMA (sandwich, non-competitive): count DIRECTLY proportional to antigen, more sensitive
Photopeak: Photoelectric interaction → all energy deposited → imaging is based on this peak
Compton edge/plateau: Compton scattering → partial energy deposited
Iodine escape peak: Photopeak – 28 keV ( 112 keV for Tc-99m)
Backscatter peak: 180° scattering from outside the crystal
Lead X-ray peak: ~72-88 keV
Sum peak: Pile-up → photopeak × 2 (at high count rate)
Compton edge + backscatter peak = photopeak energy (Tc-99m: ~50 + ~90 keV; Cs-137: 478 + 184 keV)
%FWHM varies as ≈ 1/√E → energy resolution worsens at low energy (Tl-201 > Tc-99m > I-131)
Standard: Photopeak ± 10% = 20% window
Tc-99m: 126-154 keV
I-131: 328-400 keV
Tl-201: 70 keV-centred 30% window (~60-81 keV) + a 20% window at 167 keV
Narrow window → contrast↑, sensitivity↓
Wide window → sensitivity↑, contrast↓
Standard deviation: σ = √N
Relative standard deviation: σ/N = 1/√N
95% confidence interval: N ± 2√N
99% confidence interval: N ± 2.58√N (±3√N ≈ 99.7%)
If you increase the count 4 times → the standard deviation increases 2 times → the relative standard deviation halves
Paralysable system: Count rate↑↑ → paradoxical fall in count (paralysis) → DANGEROUS (high radiation appears as a low count)
Non-paralysable system: Count rate↑↑ → plateau (the count does not rise but does not fall either)
Gamma camera: Paralysable
GM counter: Non-paralysable
Dead time correction formula: Ntrue = Nmeasured / (1 - Nmeasured × τ)
Density/Z → detection efficiency; light output → energy and timing resolution; decay time → speed
SPECT: single-piece crystal; PET: pixelated crystal array separated by reflector
SiPM/APD → Geiger mode; digital SiPM → each cell digitised separately → CTR ~130 ps
Multi-pinhole CZT (19 cameras) → no light sharing; D-SPECT → 9 rotating columns, high sensitivity
"Activity meter" instead of "dose calibrator" (the device measures activity)
Gamma probe → relative quantification by count rate; endoscopic/robotic models available
"With which device is radiopharmaceutical activity measured?" → Dose calibrator
"What type of detector is the dose calibrator?" → Well-type ionisation chamber (pressurised gas)
"Is there gas amplification in the dose calibrator?" → NO
"Gamma camera crystal?" → NaI(Tl)
"Activator of NaI(Tl)?" → Thallium (Tl)
"Most important disadvantage of NaI(Tl)?" → Hygroscopic
"Crystal thickness in the gamma camera?" → 3/8 inch (~9.5 mm)
"Modern standard crystal in PET?" → LSO/LYSO
"Crystal for TOF-PET?" → LSO/LYSO (short decay time ~40 ns)
"Why can BGO not do TOF?" → Decay time too long (300 ns)
"Detector with the best energy resolution?" → HPGe (cooling needed) → CZT in clinical use
"Photodetector in PET/MR?" → SiPM (insensitive to magnetic fields)
"Why can PMTs not be used in PET/MR?" → Sensitive to magnetic fields
"Gas-filled detector that cannot discriminate energy?" → GM counter
"Device for contamination survey?" → GM counter
"Measurement of H-3 (tritium)?" → Liquid scintillation counter (LSC)
"Counting of in vitro blood samples?" → Well counter (NaI well counter)
"Intraoperative localisation of the sentinel lymph node?" → Gamma probe
"Tc-99m energy window?" → 140 keV ± 10% (20% window)
"Iodine escape peak (Tc-99m)?" → 112 keV (140 - 28)
"Standard deviation of 10,000 counts?" → √10,000 = 100
"Gas-filled detector with the longest dead time?" → GM counter (~100-300 µs)
"What happens in a paralysable system at a high count rate?" → Paradoxical fall in count (paralysis)
"Most common source of error in the dose calibrator?" → Wrong radionuclide setting (dial setting)
"In which mode does the dose calibrator work?" → Current mode (NOT pulse mode)
"What type of detector is the well counter?" → NaI(Tl) scintillation detector (well-type)
"In which mode does the well counter work?" → Pulse mode
"Difference between the well counter and the dose calibrator?" → Well counter: scintillation, pulse mode, low activity (nCi-pCi). Dose calibrator: ionisation chamber, current mode, high activity (µCi-mCi)
"Why is a quenching gas needed in a GM counter?" → The positive ion cloud must be quenched to prevent continuous discharge → halogen (unlimited lifetime) or organic (limited lifetime ~10⁹ counts)
"Difference between the proportional counter and the GM counter?" → The proportional counter CAN discriminate energy (pulse size proportional to energy); the GM counter CANNOT
"What does yellowing of a NaI(Tl) crystal mean?" → Moisture damage (the hygroscopic crystal has absorbed moisture → the crystal is degraded → must be replaced)
"Disadvantage of LSO/LYSO?" → Natural radioactivity of Lu-176 → background activity
"What happens if the crystal thickness in the gamma camera is increased?" → Sensitivity increases (more photons absorbed) BUT intrinsic spatial resolution decreases
"What happens if the crystal thickness in the gamma camera is reduced?" → Intrinsic spatial resolution increases BUT sensitivity decreases (fewer photons absorbed)
"Energy resolution formula?" → (FWHM / E₀) × 100 (%)
"Most important factor affecting energy resolution?" → Statistical fluctuations (variation in the number of signal units produced)
"Difference between SCA and MCA?" → SCA: Single energy window (gamma camera). MCA: multichannel full spectrum (spectroscopy, radionuclide identification)
"With which device is a wipe test sample counted?" → Well counter or LSC (depending on the radionuclide)
NaI(Tl): Density 3.67 g/cm³ | Zeff 50 | Decay time 230 ns | Energy resolution ~10% (140 keV)
BGO: Density 7.13 g/cm³ | Zeff 74 | Decay time 300 ns | Energy resolution ~20% (511 keV)
LSO: Density 7.4 g/cm³ | Zeff 66 | Decay time 40 ns | Energy resolution ~10-12% (511 keV)
LYSO: Density 7.1 g/cm³ | Zeff 65 | Decay time 41 ns | Energy resolution ~10-12% (511 keV)
CZT: Density 5.8 g/cm³ | Zeff ~50 | Energy resolution ~5-6% (140 keV)
HPGe: Density 5.32 g/cm³ | Z 32 | Energy resolution ~0.2-0.5% | Cooling: 77 K (liquid nitrogen)
Gas (air): ~34 eV/ion pair
NaI(Tl) scintillation: ~20-30 eV/light photon (effective)
Semiconductor (Si): ~3.6 eV/electron-hole pair
Semiconductor (Ge): ~2.96 eV/electron-hole pair
Semiconductor (CZT): ~4.6 eV/electron-hole pair
– → In semiconductor detectors the energy needed to create one signal unit is the lowest → the most signal is produced → the best energy resolution
Most sensitive gas-filled detector → GM counter
Best energy resolution (overall) → HPGe
Best energy resolution (clinical) → CZT
Best energy resolution (gas-filled) → Proportional counter
Longest dead time → GM counter (~100-300 µs)
Shortest dead time → Semiconductor detectors (~ns)
Highest light output (classical scintillators: NaI, BGO, LSO/LYSO, GSO) → NaI(Tl) (LaBr₃/CeBr₃ and CsI(Tl) are higher; see Chapter 28)
Highest density (PET crystal) → LSO (~7.4 g/cm³)
Highest Zeff (PET crystal) → BGO (74)
Shortest decay time (PET crystal) → LSO/LYSO (~40 ns)
6. Gamma Camera and SPECT/CT
First commercial SPECT/CT: GE, 1999 → low-dose single-slice CT (~3.5 mm)
The effective dose contribution of CT is ~1-10 mSv; low-mAs CT is often sufficient for localisation/AC
HU = [(µtissue − µwater)/µwater] × 1000; HU → µ conversion is bilinear (with a phantom)
Misregistration: Respiration (SPECT averaged vs CT instantaneous), table sag, axial centre offset
Truncation, beam hardening, metal, iodinated contrast → AC artefacts
Dosimetry: VOIs are drawn on CT → transferred to SPECT; successive time points are aligned by CT–CT non-rigid registration
Dedicated brain SPECT (ring) ~3 mm; whole-body SPECT ~7-12 mm
First commercial SPECT/CT: GE, 1999 → low-dose single-slice CT (~3.5 mm)
The effective dose contribution of CT is ~1-10 mSv; low-mAs CT is often sufficient for localisation/AC
HU = [(µtissue − µwater)/µwater] × 1000; HU → µ conversion is bilinear (with a phantom)
Misregistration: Respiration (SPECT averaged vs CT instantaneous), table sag, axial centre offset
Truncation, beam hardening, metal, iodinated contrast → AC artefacts
Dosimetry: VOIs are drawn on CT → transferred to SPECT; successive time points are aligned by CT–CT non-rigid registration
Dedicated brain SPECT (ring) ~3 mm; whole-body SPECT ~7-12 mm
Inventor of the gamma camera: Hal Anger (1958)
Signal flow: Gamma photon → Collimator → Crystal (NaI(Tl)) → Light guide → PMT → Position calculation (X,Y) →
Energy analysis (Z pulse) → Image
Standard crystal thickness: 3/8 inch (~9.5 mm) → optimised for Tc-99m (140 keV)
Number of PMTs: Typically 37-91, hexagonal array
Z pulse = ΣSᵢ → represents the photon energy
Anger logic: X, Y position calculated by the weighted mean (centroid) method
Tc-99m (140 keV) → LEHR (bone, thyroid) or LEAP (dynamic studies)
Tl-201 (70-167 keV) → LEHR or LEAP
Ga-67 (93-300 keV) → ME (Medium Energy)
In-111 (171-245 keV) → ME (Medium Energy)
I-131 (364 keV) → HE (High Energy)
Thyroid (small organ) → Pinhole
The only collimator that inverts the image → Pinhole
Collimators that magnify → Pinhole (at close range) and converging
Collimator that minifies → Diverging
Distance↑ → collimator whose sensitivity stays constant → Parallel-hole
Distance↑ → collimator whose resolution and sensitivity both decrease → Pinhole
Most widely used collimator → Parallel-hole (LEHR)
Rc = d × (L + z) / L
d: hole diameter, L: hole length, z: source-collimator distance
z↑ → Rc↑ (worsens) | d↑ → Rc↑ (worsens) | L↑ → Rc↓ (improves)
If the hole diameter is increased 2 times → sensitivity increases ~4 times and resolution worsens ~2 times (sensitivity ∝ Rc²)
Pinhole/converging magnification (M) reduces the intrinsic resolution contribution to Ri/M → for a close object the system resolution may be better than the intrinsic resolution
Rs = √(Rᵢ² + Rc²)
Rc >> Rᵢ → The collimator is the limiting component
Cardiac SPECT: 180° acquisition (RAO 45° → LPO 45°), 90° (L-mode) dual-head, 64×64 matrix
General SPECT (bone, brain): 360° acquisition, 180° configuration dual-head, 128×128 matrix
Body-contour orbit → distance minimised → resolution optimised
Step-and-shoot → the most common acquisition mode
Cardiac SPECT slice planes: SA (short axis), VLA (vertical long axis), HLA (horizontal long axis)
The two basic functions of CT: Anatomical localisation + attenuation correction (CTAC)
CTAC principle: CT HU values → converted into µ values appropriate to the SPECT photon energy → attenuation map
Metallic implant → streak artefact on CT → falsely high HU → overcorrection for attenuation → hot artefact (spuriously increased uptake)
IV contrast → same mechanism → hot artefact → solution: non-contrast CT or acquire CT before contrast
Misregistration → SPECT-CT mismatch → wrong anatomical localisation + incorrect attenuation correction → cause: patient motion, respiration
NOT an advantage of SPECT/CT → increased temporal resolution (on the contrary, temporal mismatch is a disadvantage)
Component limiting total resolution → Collimator (Rc >> Rᵢ)
Total resolution formula → Rs = √(Rᵢ² + Rc²)
Most important daily quality control test → Uniformity
Measurement of intrinsic uniformity → Collimator REMOVED + point source (at 5 × FOV from the crystal)
Measurement of system (extrinsic) uniformity → Collimator FITTED + flood source
Most common cause of non-uniformity → PMT gain drift
Order of corrections → First energy → then linearity → then uniformity
Dead-time behaviour of the gamma camera → Paralysable (extendable) → paradoxical fall in counts at very high count rate (paralysis)
Sensitivity-resolution relationship → Inversely proportional (trade-off) → determined by collimator selection
LEHR: Best resolution / lowest sensitivity
LEHS: Best sensitivity / lowest resolution
LEAP: Intermediate balance
Tc-99m: 140 keV ± 10% (20% window)
I-131: 364 keV ± 10% (20% window)
Tl-201: 70 keV + 167 keV (dual window)
Ga-67: 93 + 185 + 300 keV (triple window)
In-111: 171 + 245 keV (dual window)
Narrow window → scatter rejection↑ → contrast↑ → sensitivity↓
Wide window → sensitivity↑ → scatter↑ → contrast↓
Two radionuclides on the same day: lower energy first, then higher energy (downscatter avoided; e.g. Xe-133 ventilation → Tc-99m MAA perfusion)
Thick crystal → Sensitivity↑ + intrinsic resolution↓ → for high-energy radionuclides
Thin crystal → Sensitivity↓ + intrinsic resolution↑ → for low-energy radionuclides
Standard 3/8 inch → optimal for Tc-99m (140 keV) → absorbs ~90% of the photons
The same crystal absorbs only ~30% of the 364 keV photons of I-131 (intrinsic efficiency falls with energy)
NEMA: CFOV = 75% of the linear dimensions of the UFOV; 9-point filter before calculation
Signs of crystal damage: Yellow discoloration (yellowing), cold spots, non-uniformity → cannot be repaired, must be replaced Frequently Asked "Which One?" Exam Questions – Quick Answer Cards
1. "The most important component determining the spatial resolution of the gamma camera?" → Collimator 2. "The most important component determining the sensitivity of the gamma camera?" → Collimator 3. "The most important daily quality control test?" → Uniformity 4. "The most common cause of non-uniformity?" → PMT gain drift 5. "The collimator that inverts the image?" → Pinhole 6. "The collimator used in thyroid scintigraphy?" → Pinhole 7. "The collimator whose sensitivity does not change with distance?" → Parallel-hole 8. "The collimator whose resolution and sensitivity both decrease with distance?" → Pinhole 9. "Acquisition angle in cardiac SPECT?" → 180° (RAO 45° → LPO 45°) 10. "Detector configuration in cardiac SPECT?" → 90° (L-mode) 11. "Standard crystal thickness?" → 3/8 inch (~9.5 mm) 12. "What does the Z pulse represent?" → Photon energy 13. "Dead-time type of the gamma camera?" → Paralysable 14. "Order of corrections?" → Energy → Linearity → Uniformity 15. "Metallic implant artefact in SPECT/CT?" → Hot artefact (spuriously increased uptake) 16. "Collimator for Ga-67?" → ME (Medium Energy) 17. "Collimator for I-131?" → HE (High Energy) 18. "If a high-energy radionuclide is imaged with a low-energy collimator?" → Septal penetration → star artefact
19. "Advantage of the converging collimator?" → Higher sensitivity than the parallel-hole collimator 20. "Why is the body-contour orbit preferred?" → Detector-patient distance minimised → resolution optimised
7. PET/CT and PET/MR
PET/CT ~2001 (Townsend); CT replaced the Ge-68 transmission scan, which took up to 15 min
TOF routine since 2006; LAFOV 1-2 m → ~1-2 mSv or <5 min whole body
Gating: list mode; cardiac → ECG, respiratory → pneumatic belt
PET/MR: Siemens 2011 (APD, no TOF), GE 2014 (SiPM, with TOF)
DPC: SiPM microcell binary output; energy = number of cells fired
MR coils and the table also contribute to 511 keV attenuation; CT-derived µ map in the phantom
CTDI (16/32 cm phantom, mGy) ≠ patient dose; DLP = CTDI × length
PET/CT ~2001 (Townsend); CT replaced the Ge-68 transmission scan, which took up to 15 min
TOF routine since 2006; LAFOV 1-2 m → ~1-2 mSv or <5 min whole body
Gating: list mode; cardiac → ECG, respiratory → pneumatic belt
PET/MR: Siemens 2011 (APD, no TOF), GE 2014 (SiPM, with TOF)
DPC: SiPM microcell binary output; energy = number of cells fired
MR coils and the table also contribute to 511 keV attenuation; CT-derived µ map in the phantom
CTDI (16/32 cm phantom, mGy) ≠ patient dose; DLP = CTDI × length
Iterative reconstruction → noise↓, resolution preserved, dose↓; PCCT → photon counting, spectral imaging
MR: ω = γB₀; clinical 1.5-3 T; k-space → Fourier transform
Molecular sensitivity: PET > SPECT >> MRI
Threshold energy for positron emission: 1.022 MeV
Annihilation photon energy: 511 keV (each)
Total annihilation energy: 1.022 MeV
Angle between the two photons: ~180°
Angular deviation (acolinearity): ±0.25°
Effect of acolinearity on resolution: ~2 mm (in a PET of 80 cm diameter)
Theoretical resolution limit of PET: ~2-3 mm
F-18: 0.6 mm → BEST resolution
C-11: 1.1 mm
N-13: 1.5 mm
O-15: 2.5 mm
Ga-68: 2.9 mm
Rb-82: 5.9 mm → WORST resolution
Rule to memorise: energy↑ → range↑ → resolution↓
True: Same event, correct LOR → the desired event
Scatter: Same event, scattered photon → wrong LOR → loss of contrast
Random: Different events, chance pairing → wrong LOR → homogeneous noise
Multiple: 3+ photons at once → event rejected
Random correction method: Delayed window
Random ∝ A² (quadratic), True ∝ A (linear)
Highest stopping power: BGO (highest effective Z)
Most widely used: LSO / LYSO
Most suitable for TOF-PET: LSO / LYSO (short decay time ~40 ns)
Why BGO is not suitable for TOF: Long decay time (300 ns)
Disadvantage of LSO: Natural Lu-176 radioactivity (intrinsic background)
Best energy resolution: NaI(Tl) (~8%) → but insufficient stopping power for PET
Light detector in PET/MR: SiPM (insensitive to magnetic fields)
Why PMTs cannot be used in PET/MR: Sensitive to magnetic fields
PET: Electronic collimation (coincidence detection) → NO physical collimator
SPECT: Physical collimator required
PET sensitivity ~10-100 times higher than SPECT
PET spatial resolution: ~4-6 mm (clinical) vs SPECT: ~8-12 mm
PET: 511 keV photons vs SPECT: the gamma energy of the radionuclide (usually 70-364 keV)
Position calculation: Δx = c × Δt / 2
SNR gain: √(D / Δx)
Most marked advantage in obese patients (D large → gain large)
Required for TOF: Fast crystal (LSO/LYSO) + SiPM + fast electronics
Current timing resolution: 200-400 ps
200 ps → Δx = 3 cm
400 ps → Δx = 6 cm
TOF does not directly improve spatial resolution (Δx is at the cm level); the gain is in SNR/effective sensitivity, contrast and lesion detectability
PET energy window typically ~425/435-650 keV (LSO/LYSO); if the lower threshold is lowered, scatter acceptance increases
Bilinear transformation: conversion from CT energy (~70-140 keV) to the µ value at 511 keV
SUVbw falsely high in an obese patient → solution: SUVlean
HU > 0: Different curve (soft tissue-bone)
Metallic implant → falsely high HU → CTAC overcorrection → hot artefact
Contrast medium → falsely high HU → hot artefact
Respiratory misregistration → cold band at the diaphragm base or hot artefact at the lung base
Verification: Always compare with NAC (non-attenuation-corrected) images
NAC image: skin and lung activity high, centre of the body faint/periphery bright
CT parameters: mAs↑ → dose↑ linearly, noise ∝ 1/√mAs, contrast unchanged; kVp↑ → noise↓, contrast↓, dose↑; pitch↑ → dose↓
Most important technical challenge: MRAC (MR-based attenuation correction)
The MRAC problem: bone and air are signal-free on MR → cannot be distinguished → bone attenuation is undercorrected
Most common MRAC method: Dixon-based segmentation (4 classes: air, lung, fat, soft tissue)
Methods that solve the bone problem: UTE/ZTE, atlas-based, deep learning
Light detector in PET/MR: SiPM (the PMT cannot work in the magnetic field)
Advantages of PET/MR: Superior soft-tissue contrast, lower radiation dose, simultaneous acquisition, functional MR
Areas where PET/CT is superior: Lung nodules, cortical bone lesions, speed/practicality, RT planning
Strong indications for PET/MR: Neurology, paediatric oncology, pelvic tumours, head and neck, liver
SUV formula: Tissue activity concentration / (Injected activity / Body weight)
Most common variant: SUVmax (single voxel, operator-independent)
PERCIST variant: SULpeak (lean body mass + 1 cm³ spherical VOI)
"Why is SUV falsely high in an obese patient?" → Fat does not take up FDG but is included in the weight → use SUVlean
Increases SUV: Long uptake time, inflammation, high tumour grade
Decreases SUV: Hyperglycaemia (the most important!), small lesion (PVE), extravasation, short uptake time
Partial volume effect: Lesion < 2-3 × resolution (~8-10 mm) → SUV lower than it is
TLG = MTV × SUVmean
Standard uptake time: 60 ± 10 minutes
Dual-time-point imaging: the late SUV usually rises in malignancy, but it also rises in inflammation → limited value in differentiation
Fasting: Minimum 4-6 hours
Upper limit of blood glucose: 150-200 mg/dL
Hyperglycaemia → tumour SUV↓ → false negative
Insulin should not be given immediately before FDG → muscle uptake↑ (FDG ≥4 hours after short-acting insulin)
Reducing brown fat (BAT): Warm environment, propranolol, diazepam
BAT locations: Supraclavicular, cervical, paravertebral, mediastinal → bilateral symmetrical
After G-CSF: Wait at least 2 weeks (bone marrow uptake)
After chemotherapy: At least 2-3 weeks (ideally 6 weeks)
After radiotherapy: At least 2-3 months
Rebound thymic hyperplasia: Diffuse mediastinal uptake in a young patient after chemotherapy → false positive
2D: Septa present → scatter↓, randoms↓ → but sensitivity↓ → no longer used
3D: No septa → sensitivity ~4-8-fold↑ → but scatter↑ (30-40%), randoms↑ → the standard today
"Is there a collimator in PET?" → NO (electronic collimation)
"With which radionuclide is PET resolution best?" → F-18
"With which radionuclide is PET resolution worst?" → Rb-82
"Why is TOF more advantageous in an obese patient?" → D large → √(D/Δx) large
"How do you verify a CTAC artefact?" → Compare with NAC images
"Why is bone a problem in PET/MR?" → Bone is signal-free on MR → confused with air → undercorrection
"What happens in hyperglycaemia?" → Tumour SUV↓ → false negative
HU ≤ 0: One curve (air-soft tissue)
8. Image Reconstruction and Processing
Photopeak window typically 10-20%; for 128 × 128 SPECT, 120 projections over 360° are sufficient
Static / dynamic (1-5 s frames) / list mode (event-based, clinical in PET) / gated (ECG, respiratory)
In PET, attenuation → depends on body size; in SPECT → depends on depth (Tc-99m brain: counts may fall by >4-fold)
Partial volume → <2 × FWHM; more pronounced in SPECT; large ROI → total activity correct, mean concentration low
Patlak → Ki (irreversible); Logan → VT (reversible); 2-compartment/4-constant → specific binding
FBP: Analytical solution → fast → 1/r correction with ramp filter → noise-sensitive → streak artefacts → may produce negative values → limited modelling of physical factors → limited use today
MLEM: Iterative → Poisson statistics → multiplicative update → no negative values → all projection data in every iteration → very slow → not suitable for clinical use
Photopeak window typically 10-20%; for 128 × 128 SPECT, 120 projections over 360° are sufficient
Static / dynamic (1-5 s frames) / list mode (event-based, clinical in PET) / gated (ECG, respiratory)
In PET, attenuation → depends on body size; in SPECT → depends on depth (Tc-99m brain: counts may fall by >4-fold)
Partial volume → <2 × FWHM; more pronounced in SPECT; large ROI → total activity correct, mean concentration low
Patlak → Ki (irreversible); Logan → VT (reversible); 2-compartment/4-constant → specific binding
FBP: Analytical solution → fast → 1/r correction with ramp filter → noise-sensitive → streak artefacts → may produce negative values → limited modelling of physical factors → limited use today
MLEM: Iterative → Poisson statistics → multiplicative update → no negative values → all projection data in every iteration → very slow → not suitable for clinical use
OSEM: Accelerated version of MLEM → division into subsets → acceleration ≈ number of subsets → standard today → typical: 2-4 iterations × 8-16 subsets
Effective iterations = number of iterations × number of subsets
Iterations↑ → resolution↑, contrast↑, noise↑
Iterations↓ → noise↓, resolution↓, contrast↓
Chang: Post-reconstruction → uniform µ assumption → simple → specific to SPECT → inaccurate in the thorax (lung–soft tissue difference)
CTAC: Intra-reconstruction → non-uniform µ map → CT HU → bilinear conversion → voxel-based → most accurate → standard in PET/CT and SPECT/CT
Transmission source: Ge-68 or Cs-137 → old PET method → no longer used
MRAC: In PET/MR → Dixon segmentation → bone problem → solved with UTE/ZTE/atlas/deep learning
Attenuation correction is mandatory in PET (photon pair attenuation, independent of source position)
Attenuation correction is recommended in SPECT but not mandatory
Tc-99m (140 keV) µ ≈ 0.15 cm⁻¹ | 511 keV µ ≈ 0.096 cm⁻¹
SPECT: TEW (triple energy window) → 3 windows → trapezoidal approximation → standard
PET: SSS (Single Scatter Simulation) → Klein-Nishina → analytical → standard
Scatter fraction: SPECT ~30-40% | 3D PET ~30-50% | 2D PET ~15-20%
Cardiac gating: ECG → R-R interval → 8 or 16 frames → LVEF = (EDV-ESV)/EDV × 100
Respiratory gating: Respiratory sensor → 4-10 phases → most stable phase: end-expiration
Dual gating: Cardiac + respiratory → best correction → too many bins → noise → limited clinical use
Arrhythmia management: Beat rejection (±20% acceptance window)
Tachycardia → short R-R → short frame duration → temporal sampling becomes difficult
Arrhythmia → rejected beats → loss of counts, gating artefact
Ramp filter: Specific to FBP → H(f) = |f| → 1/r correction → high-frequency amplification → noise↑ → not used alone → window function needed
Butterworth: Most common → cutoff frequency + order → cutoff frequency↑ → resolution↑, noise↑
Gaussian: Common in PET → FWHM parameter → FWHM↑ → smoothing↑ → no ringing artefact
Hanning/Hamming: Window functions → used with the ramp in FBP
Order of smoothing at the same cutoff frequency: Ramp < Shepp-Logan < Hamming < Hanning < Parzen (Parzen smoothest, lowest resolution)
Prefiltering (to 2D projections before reconstruction) vs postfiltering (to the 3D volume after reconstruction)
Low frequencies = signal (general structure) | High frequencies = detail + noise
Pixel size ≤ 1/2 - 1/3 of FWHM (Nyquist criterion)
Nyquist frequency = 1 / (2 × pixel size)
SPECT matrix: 64 × 64 or 128 × 128
PET matrix: 128 × 128 – 400 × 400
Pixel depth: byte (8-bit) → at most 255 counts/pixel; word (16-bit) → 65,535
Pixel size = FOV / (matrix × zoom) → zoom makes the pixel smaller and narrows the displayed field
Number of SPECT projections: 60-128 (360°)
Too few projections → streak artefacts
Preferred orbit: Body contouring
Step-and-shoot vs continuous: Step-and-shoot → less angular blurring
Improves resolution → partial volume effect decreases → SUV may increase
Most important artefact: Gibbs artefact (Gibbs ringing) → ring at the edges of hot spots
Consistent reconstruction parameters must be used in follow-up studies
Point source → sinusoidal curve
Point source at the centre of rotation → straight vertical line
Sinogram = 2D matrix display of projection data from all angles (x: detector position, y: angle)
The sinogram is the input data of the reconstruction algorithm
1D Fourier transform of a projection profile = a line through the 2D Fourier space of the image at that angle
It is the mathematical basis of FBP
Thanks to this theorem, the frequency-space representation is obtained from projection data → the image is formed by the inverse Fourier transform
Intra-reconstruction correction: CTAC (included in the system matrix in iterative reconstruction) → applied during reconstruction
Post-reconstruction correction: Chang method → the image is formed first, then multiplied by the correction matrix
Ramp filter ≠ Butterworth filter: Ramp → 1/r correction (specific to FBP); Butterworth → noise reduction (smoothing)
MLEM ≠ OSEM: MLEM → all projection data in every iteration → slow; OSEM → division into subsets → fast
TEW ≠ SSS: TEW → SPECT scatter correction; SSS → PET scatter correction
Noise ≠ Resolution: Iterations↑ → both increase (trade-off); cutoff frequency↓ → both decrease
Effective iterations = Number of iterations × Number of subsets
LVEF = (EDV − ESV) / EDV × 100
Nyquist frequency = 1 / (2 × pixel size)
Pixel size ≤ FWHM / 2 (ideal: FWHM / 3)
Chang correction factor: C(x,y) = 1 / [1/N × Σ e−µ·dᵢ]
Butterworth: H(f) = 1 / √[1 + (f/fc)2n]
Gaussian: H(f) = e−2π²σ²f², FWHM = 2.355 × σ
Ramp: H(f) = |f|
PET attenuation correction factor: ACF = e^(+µ·D) → independent of source position
1. The standard reconstruction algorithm in SPECT and PET today → OSEM 2. Attenuation correction in PET → mandatory (CTAC standard) 3. Attenuation correction in SPECT → recommended (Chang or CTAC) 4. SPECT scatter correction → TEW 5. PET scatter correction → SSS 6. Most common filter → Butterworth 7. Number of frames in gated SPECT → 8 or 16 8. Most stable phase in respiratory gating → end-expiration 9. Artefact of PSF modelling → Gibbs ringing 10. Point source in the sinogram → sinusoidal curve
9. Image Quality and Artefacts
Spatial resolution is measured by FWHM → smaller FWHM = better resolution
System resolution = √(R²intrinsic + R²collimator) → collimator resolution dominates
The factor that most affects collimator resolution → source–collimator distance
Sensitivity and resolution are inversely related (trade-off)
With a parallel-hole collimator, sensitivity is independent of distance; resolution worsens with distance
Dominant noise source in nuclear medicine → statistical (Poisson) noise (σ = √N)
SNR = √N → if counts increase 4-fold, SNR increases 2-fold
Spatial resolution is measured by FWHM → smaller FWHM = better resolution
System resolution = √(R²intrinsic + R²collimator) → collimator resolution dominates
The factor that most affects collimator resolution → source–collimator distance
Sensitivity and resolution are inversely related (trade-off)
With a parallel-hole collimator, sensitivity is independent of distance; resolution worsens with distance
Dominant noise source in nuclear medicine → statistical (Poisson) noise (σ = √N)
SNR = √N → if counts increase 4-fold, SNR increases 2-fold
Rose criterion: CNR ≥ 3-5 → required for reliable lesion detection
Partial volume effect: Lesion < 2-3 × FWHM → in a hot lesion SUV↓ (spill-out), in a cold lesion SUV↑ (spill-in)
Recovery coefficient (RC) = measured / true concentration; in a small lesion RC < 1 → corrected value = measured / RC
The system MTF is the product of the component MTFs → the total MTF is lower even than the weakest component
FWTM/FWHM > ~1.83 (Gaussian) → long tail → septal penetration/scatter
With the same total counts, the relative noise of a SPECT slice is higher than planar (reconstruction amplifies noise)
Upward creep: Gradual upward shift of the diaphragm after exercise → inferior wall artefact → solution: wait 15-30 min or prone position
Breast attenuation: Woman → fixed anterior wall defect
Diaphragmatic attenuation: Man → fixed inferior wall defect
Distinguishing attenuation artefact from true defect: 1) CTAC, 2) Prone position, 3) Gated analysis (wall motion/thickening)
Brown adipose tissue (BAT): Symmetric cervical/supraclavicular FDG uptake → reduced with propranolol, warm environment
Suppression of myocardial FDG: Prolonged fasting (≥12-18 hours) + high-fat diet
Ring artefact (SPECT) → non-uniformity (PMT gain difference, crystal defect)
COR error: Small → blurring; large → donut artefact (different from ring artefact!)
PMT failure: Focal cold (gain loss) or hot (gain increase) area on the flood image
Energy window shift: General loss of counts, non-uniformity → prevented by daily peaking
Metallic implant: High HU → overcorrection → spuriously increased uptake → verify with the NAC image
IV contrast: High intravascular HU in the bolus phase → spuriously increased uptake (especially SVC, subclavian vein)
Oral contrast: Dense barium → spuriously increased uptake → negative oral contrast (water) should be preferred
Misregistration: Respiratory motion → most pronounced at the level of the diaphragm → banana artefact (curved cold area at the liver dome)
Truncation: Obese patient / arms at the sides → extending beyond the FOV → spuriously increased uptake at the edges
Gold-standard verification for all CTAC artefacts: review of the NAC (non-attenuation-corrected) images
Random coincidence: Proportional to the square of activity (R = 2τ·S₁·S₂)
True coincidence: Directly proportional to activity
Scatter coincidence: Directly proportional to activity; markedly increased in 3D mode (30-50% vs 15-20% in 2D)
Dead time: Loss of counts at high activity → paradoxical fall in counts in the paralyzable model
Parallax error (DOI): Loss of resolution at the edge of the FOV → radial elongation
The most important patient factor affecting SUV: Blood glucose → hyperglycaemia → tumour SUV↓
Upper limit of blood glucose before PET: 150-200 mg/dL
Star artefact: Star-shaped streaks around an intense source in FBP → solution: iterative reconstruction (OSEM)
Ring artefact: Non-uniformity → solution: daily flood QC, PMT calibration
Body contouring orbit: Superior to a circular orbit → detector close to the patient at every angle → resolution↑
Angular sampling: Too few projections → streak artefacts
1. Suspected CTAC artefact → review the NAC images 2. Attenuation artefact vs true defect (cardiac) → CTAC + prone position + gated analysis 3. Suspected misregistration → emission–CT fusion check 4. Suspected ring artefact → flood (uniformity) quality control 5. Suspected COR error → point source COR test 6. Suspected BAT uptake → check for fat density on CT + symmetric pattern
10. Radiation Dosimetry and Safety
Effective dose cannot be measured → H*(10) (ambient), Hp(10) (whole body), Hp(0.07) (skin), Hp(3) (eye lens)
Controlled area vs supervised area
Category A: likely to receive >6 mSv/year effective, >15 mSv/year eye lens, >150 mSv/year skin/extremity; Category B: those who may exceed the public limit
Absorbed dose: Gray (Gy) = 100 rad → a physical quantity, does not take radiation type into account
Equivalent dose: Sievert (Sv) = 100 rem → corrected with the radiation weighting factor (wR)
Effective dose: Sievert (Sv) → corrected with the tissue weighting factor (wT) → indicator of stochastic risk
For photons and beta wR = 1 → absorbed dose (Gy) = equivalent dose (Sv) numerically
Effective dose cannot be measured → H*(10) (ambient), Hp(10) (whole body), Hp(0.07) (skin), Hp(3) (eye lens)
Controlled area vs supervised area
Category A: likely to receive >6 mSv/year effective, >15 mSv/year eye lens, >150 mSv/year skin/extremity; Category B: those who may exceed the public limit
Absorbed dose: Gray (Gy) = 100 rad → a physical quantity, does not take radiation type into account
Equivalent dose: Sievert (Sv) = 100 rem → corrected with the radiation weighting factor (wR)
Effective dose: Sievert (Sv) → corrected with the tissue weighting factor (wT) → indicator of stochastic risk
For photons and beta wR = 1 → absorbed dose (Gy) = equivalent dose (Sv) numerically
For alpha wR = 20 → 1 Gy of alpha = 20 Sv equivalent dose
Exposure (roentgen) is valid only for photons and in air
In air 1 R ≈ 0.87 rad; in bone the f factor (rad/R) rises markedly at low photon energies (photoelectric, Z³)
Effective dose per MBq: Tl-201 (~0.14-0.22) and Ga-67 (~0.10 mSv/MBq) are much higher than most Tc-99m agents (~0.005-0.01)
Highest wT (0.12): Bone marrow, colon, lung, stomach, breast, remainder tissues
Gonad wT: 0.20 in ICRP 60 → 0.08 in ICRP 103 (reduced)
Breast wT: 0.05 in ICRP 60 → 0.12 in ICRP 103 (raised)
Total wT = 1.00
Dose = Cumulated activity (Ã) × S value
Cumulated activity = area under the activity–time curve = total number of decays
Effective half-life: Teff = (Tphys × Tbiol)/(Tphys + Tbiol) → always shorter than both, closer to the shorter one
S value: A physical parameter depending on radionuclide emissions, organ geometry and mass
Occupational: 20 mSv/year (5-year average; ≤50 mSv in a single year)
Public: 1 mSv/year
Eye lens (ICRP 118): 20 mSv/year average (old: 150 mSv/year)
Skin/extremity: 500 mSv/year
Fetal: 1 mSv (ICRP) or 5 mSv (NRC) for the whole pregnancy
Dose limits do not apply to patients → managed by justification and optimisation
TLD material: LiF (tissue-equivalent)
OSL material: Al₂O₃:C → can be read multiple times (information is not erased)
Film badge: No instant reading, sensitive to heat/humidity
Instant reading: Pocket ionisation chamber or electronic personal dosimeter (EPD)
Lead apron + single dosimeter → outside the apron, at collar level
Gold standard in biological dosimetry: Dicentric chromosome analysis
Dicentrics/rings are unstable (lost with division); past exposure → FISH analysis of stable translocations
ALARA: As Low As Reasonably Achievable
The protection triad: Time, Distance, Shielding
Inverse square law: Distance 2× → dose decreases 4×
Beta shielding: Low Z (Perspex) → to prevent bremsstrahlung
Shielding for P-32 → Perspex (NOT lead)
PET (511 keV) syringe shields → tungsten (high density)
Radioiodine solution is volatile: acidic pH/oxidation increase volatility → alkaline pH + reducing agent, fume hood
White-I: Surface ≤0.005 mSv/h, TI = 0
Yellow-II: Surface ≤0.5 mSv/h, 1 m ≤0.01 mSv/h, TI ≤1.0
Yellow-III: Surface ≤2 mSv/h, 1 m ≤0.1 mSv/h, TI ≤10.0
Radiation Area: 0.05 mSv/h @ 30 cm
High Radiation Area: 1 mSv/h @ 30 cm
Very High Radiation Area: 5 Gy/h @ 1 m
Removable contamination: ≤200 (I-131) / ≤2000 (Tc-99m) dpm/100 cm²
Skin decontamination: Warm water + soap, DO NOT scrub hard
Surface decontamination: Wipe from the outside inwards
Major spill: Leave the area → report to the RSO
I-131 → KI (potassium iodide)
Cs-137 → Prussian blue
Plutonium/Americium → DTPA
Tritium → Plenty of water (forced diuresis)
I-131 is absolutely contraindicated in pregnancy → fetal thyroid damage (from week 10-12 onwards)
Termination of pregnancy is not recommended below 50 mGy
Breastfeeding must be stopped permanently after I-131
Tc-99m compounds: Most require no interruption; 12 hours for pertechnetate and MAA
Ga-67: ≥3-4 weeks (stopped in practice), Tl-201: 48 hours
Activity-based: ≤33 mCi (1.22 GBq)
Dose-rate-based: ≤7 mR/h @ 1 m
Patient-specific: Dose to others ≤5 mSv (child/pregnant woman: ≤1 mSv ICRP/IAEA constraint)
Deviation of more than ±20% in a therapeutic dose
Wrong patient, wrong radiopharmaceutical, wrong route of administration
Reporting: to the NRC by the next calendar day, written report within 15 days
The patient should be informed within 24 hours
11. Radionuclide Production and Generators
The correct term is "radionuclide"; notation ¹⁸F, [¹⁸F]FDG
Half-life ↔ biological process: minutes (O-15, Rb-82), hours (F-18, Ga-68, Tc-99m), days (Zr-89, In-111)
Therapy: decay type, energy, half-life, LET and the whole decay chain (Ac-225 → 4 α)
Primary precursors that can be used directly as agents: [¹⁸F]fluoride, [⁹⁹ᵐTc]pertechnetate
Purification: HPLC/SPE; sterilisation: 0.22 µm filter and/or autoclave
Reactor products → neutron-rich → beta-minus (β⁻) decay
Cyclotron products → proton-rich → positron (β⁺) or electron capture (EC) decay
The correct term is "radionuclide"; notation ¹⁸F, [¹⁸F]FDG
Half-life ↔ biological process: minutes (O-15, Rb-82), hours (F-18, Ga-68, Tc-99m), days (Zr-89, In-111)
Therapy: decay type, energy, half-life, LET and the whole decay chain (Ac-225 → 4 α)
Primary precursors that can be used directly as agents: [¹⁸F]fluoride, [⁹⁹ᵐTc]pertechnetate
Purification: HPLC/SPE; sterilisation: 0.22 µm filter and/or autoclave
Reactor products → neutron-rich → beta-minus (β⁻) decay
Cyclotron products → proton-rich → positron (β⁺) or electron capture (EC) decay
Fission → high specific activity (carrier-free)
(n,γ) reaction → low specific activity (target and product the same element → chemical separation not possible)
(n,p) reaction → high specific activity (target and product different elements → chemical separation possible)
Primary production of Mo-99: U-235 fission (reactor) → fission yield ~6.1%
HEU → LEU conversion: International pressure because of the risk of nuclear weapons proliferation
F-18: ¹⁸O(p,n)¹⁸F → O-18-enriched water target → T½ = 109.8 min
C-11: ¹⁴N(p,α)¹¹C → N₂ gas target → T½ = 20.4 min
N-13: ¹⁶O(p,α)¹³N → water target → T½ = 9.97 min
O-15: ¹⁵N(p,n)¹⁵O or ¹⁴N(d,n)¹⁵O → T½ = 2.04 min → on-site cyclotron essential
F-18 has the lowest positron energy (Emax = 0.634 MeV) → best PET spatial resolution
Rb-82 has the highest positron energy (Emax = 3.35 MeV) → worst PET spatial resolution
Kryptofix 222 in FDG synthesis → phase-transfer catalyst → toxic → must be tested in quality control
Dry conditions are needed in FDG synthesis → water inhibits nucleophilic substitution
FDG radiochemical purity limit: ≥95%
Mo-99/Tc-99m: Transient equilibrium | Elution with saline | Al₂O₃ column | Lifetime: ~1-2 weeks | Tc-99m elutes as pertechnetate (TcO₄⁻)
Ge-68/Ga-68: Secular equilibrium | Elution with 0.1 M HCl | TiO₂ or SnO₂ column | Lifetime: ~9-12 months
Sr-82/Rb-82: Secular equilibrium | Elution with saline | SnO₂ column | Lifetime: ~4-8 weeks | Automated infusion system needed (T½ = 75 s)
Transient equilibrium: T½(parent)/T½(daughter) ratio relatively small (~10-100) → daughter activity temporarily exceeds parent activity
Secular equilibrium: T½(parent)/T½(daughter) ratio very large (>100) → daughter activity becomes equal to parent activity
Mo-99 breakthrough limit: ≤0.15 µCi Mo-99/mCi Tc-99m → measured by the lead pot method
As the eluate stands the Mo-99/Tc-99m ratio rises (Mo-99 decays more slowly) → the breakthrough limit must also be met at the time of administration
Al breakthrough limit: ≤10 µg Al/mL → measured by a colorimetric test (aurintricarboxylic acid)
High Al → flocculation (large particles) in Tc-99m sulphur colloid → lung uptake; liver uptake with MDP
If the generator is not eluted for a long time → Tc-99 builds up → specific activity falls → labelling efficiency decreases
Maximum Tc-99m build-up after elution: ~23 hours (~4 × T½)
Tc-99m/Mo-99 activity ratio in transient equilibrium: theoretical ~1.10; with branching (87.5%) in practice ~0.96 (does not exceed)
Sr-82 breakthrough limit: ≤0.02 µCi Sr-82/mCi Rb-82
Sr-85 contamination limit: ≤0.2 µCi Sr-85/mCi Rb-82
Sr-82 breakthrough → increases bone dose (strontium is a calcium analogue → accumulates in bone)
Daily quality control is mandatory
Ge-68 breakthrough limit: ≤0.001% Ge-68/Ga-68
Measurement: Wait 48 hours after elution → Ga-68 decays → the remaining activity is Ge-68
Ga-68 can also be produced in a cyclotron by ⁶⁸Zn(p,n)⁶⁸Ga → no risk of Ge-68 breakthrough
Metal contamination (Fe, Cu, Zn) → lowers peptide labelling efficiency → purification with a cation-exchange cartridge
Y-90 and P-32 → cannot be imaged directly (only indirectly via bremsstrahlung)
Y-90: T½ = 2.67 days, Emax = 2.28 MeV → microspheres (radioembolisation), Zevalin
P-32: T½ = 14.3 days, Emax = 1.71 MeV → polycythaemia vera
Alpha emitter (FDA-approved): Ra-223 (Xofigo®) → bone metastases (mCRPC)
Theranostic agents: Lu-177 → both beta (therapy) and gamma (113, 208 keV → SPECT imaging)
I-131 → both beta (therapy) and gamma (364 keV → scintigraphy)
Definition: Radioactivity per unit mass
High specific activity → fission, (n,p), cyclotron production
Low specific activity → (n,γ) reaction
In receptor-based imaging, low specific activity → cold molecules block the receptors → target/background ratio falls
Mo-99 produced by (n,γ) is not ideal for a generator → low specific activity → not enough Mo-99 can be loaded onto the alumina column
Dilution lowers the radioactive concentration (mCi/mL) but does not change specific activity
I-123: The Te-124(p,2n) route contains I-124 impurity; the Xe-124 → Xe-123 → I-123 route gives high purity free of I-124
Mo-99, I-131, Xe-133, Cr-51, P-32, Sr-89, Sm-153, Lu-177, Y-90, Re-186, Er-169, Ho-166
F-18, C-11, N-13, O-15, Ga-67, I-123, In-111, Tl-201, Cu-64, Zr-89
"Reactor = Neutron = Neutron-rich = Beta-minus"
"Cyclotron = Proton = Proton-rich = Positron/EC"
"Same element = No separation = Low specific activity" → (n,γ)
"Different element = Separation possible = High specific activity" → fission, (n,p), cyclotron
Generator elution mnemonic: "Mo-Tc SALINE, Ge-Ga HCL, Sr-Rb SALINE"
Generator equilibrium mnemonic: "Mo-Tc TRANSIENT, Ge-Ga SECULAR, Sr-Rb SECULAR"
Generator column mnemonic: "Mo-Tc ALumina, Ge-Ga TItanium, Sr-Rb TIN"
12. Radiopharmaceuticals
<40 kDa → capillary extravasation; ≤60 kDa → glomerular filtration; IgG → long blood half-life via FcRn
EPR → non-specific accumulation of large molecules in tumour
DRL → typical diagnostic activity recommended in a standard patient
GLP (non-clinical) vs GMP (production); if terminal sterilisation is not possible, aseptic production + 0.22 µm filtration
The sterility test is mostly retrospective; the Production and QC managers are independent; the batch is released by the Qualified Person
The reducing agent in Tc-99m kits = stannous chloride (SnCl₂) → reduces pertechnetate from +7 to a lower oxidation state → forms complexes with ligands
Excess SnCl₂ → formation of colloidal Tc; insufficient SnCl₂ → free pertechnetate remains
<40 kDa → capillary extravasation; ≤60 kDa → glomerular filtration; IgG → long blood half-life via FcRn
EPR → non-specific accumulation of large molecules in tumour
DRL → recommended typical diagnostic activity in a standard patient
GLP (non-clinical) vs GMP (production); if terminal sterilisation is not possible, aseptic production + 0.22 µm filtration
Sterility testing is mostly retrospective; Heads of Production and QC are independent; the Qualified Person releases the batch
Reducing agent in Tc-99m kits = stannous chloride (SnCl₂) → reduces pertechnetate from +7 to a lower oxidation state → forms a complex with ligands
Excess SnCl₂ → colloidal Tc formation; insufficient SnCl₂ → free pertechnetate remains
Tc-99m MIBI and MAG3 kits require boiling; other kits are usually prepared at room temperature
Presence of oxygen → SnCl₂ oxidation → labelling efficiency falls → kits are stored under nitrogen
Tc-99m sulphur colloid: Tc is not reduced → precipitates as Tc₂S₇ (+7)
Transchelation intermediate ligands: tetrofosmin (gluconate), MAG3 (tartrate), MIBI (citrate)
MAG3 kit: ~2 mL filtered air into the vial (excess Sn²⁺ is oxidised) + 10 min boiling water bath (benzoyl group is cleaved)
HMPAO: eluate must be ≤2 hours old and the generator eluted within the last 24 hours (Tc-99 build-up impairs labelling); without stabiliser use within 30 min
Capillary blockade: Tc-99m MAA (pulmonary arterioles, 10-100 µm)
Phagocytosis (RES): Tc-99m sulphur colloid (hepatic Kupffer cells)
Active transport: Tl-201 (Na⁺/K⁺-ATPase), I-131/I-123 (NIS); FDG enters by GLUT-facilitated diffusion (metabolic trapping)
Mitochondrial membrane potential: Tc-99m MIBI, Tc-99m tetrofosmin
Chemisorption: Tc-99m MDP/HDP, F-18 NaF (bone surface)
Metabolic trapping: FDG (hexokinase), Tc-99m HMPAO (glutathione → conversion to hydrophilic form)
Compartmental distribution: Tc-99m DTPA (GFR), Tc-99m labelled red cells (blood pool)
Receptor binding: DOTATATE (SSTR2), PSMA, MIBG (uptake-1/NET), OctreoScan (SSTR2)
Tubular secretion: Tc-99m MAG3 (98% tubular secretion)
Tubular binding (cortical fixation): Tc-99m DMSA (proximal tubule)
In vivo: 75-80% (lowest, most free pertechnetate)
Modified in vivo (in vivtro): 85-90%
In vitro (UltraTag®): >95% (gold standard → preferred for MUGA and GI bleeding)
Metabolic trapping: GLUT → hexokinase → FDG-6-phosphate (low glucose-6-phosphatase → trapping)
Patient preparation: 4-6 hours fasting, blood glucose <150-200 mg/dL, ≥4 hours after insulin
Insulin-sensitive GLUT-4 in myocardium/skeletal muscle → the fed state/insulin increases muscle and myocardial uptake, leaving less FDG for the tumour
False-negative tumours: Lepidic adenocarcinoma, RCC, HCC, prostate Ca, low-grade lymphoma, well-differentiated NET, mucinous tumours
False positives: Infection/inflammation, sarcoidosis, granulomatous disease, brown fat, muscle activity, postoperative changes
Reducing brown fat uptake: Warm environment, propranolol (20 mg orally, 1 hour before), diazepam
Ga-68 DOTATATE (diagnosis) → Lu-177 DOTATATE (therapy/PRRT) → NET
Ga-68/F-18 PSMA (diagnosis) → Lu-177 PSMA (therapy) → mCRPC
Theranostics = diagnostic + therapeutic pair using the same molecular target
I-131: β⁻ + gamma, T½ = 8 days → thyroid cancer, hyperthyroidism
Lu-177: β⁻ + gamma, T½ = 6.65 days → PRRT (DOTATATE), PSMA therapy
Y-90: Pure β⁻ (no gamma), T½ = 64.1 hours → radioembolisation, radioimmunotherapy (Zevalin)
Ra-223: Alpha, T½ = 11.4 days → mCRPC with bone metastases (survival benefit!)
Sr-89: Almost pure β⁻, T½ = 50.5 days → bone pain palliation (long T½ → more toxicity)
Sm-153: β⁻ + gamma, T½ = 46.3 hours → bone pain palliation (short T½ → less toxicity)
Only Ra-223 has shown a survival benefit (ALSYMPCA trial)
Sr-89 and Sm-153 → palliative only, no survival benefit
Ra-223 → alpha emitter (high LET, short range 100 µm)
Ra-223 → indicated only in mCRPC with bone metastases (visceral metastases → contraindicated)
Pre-treatment Tc-99m MAA shunt study is mandatory
Lung shunt >20% → contraindicated
Lung shunt 10-20% → dose reduction
GI shunt → prophylactic coil embolisation
TheraSphere® (glass) vs SIR-Spheres® (resin) → resin has a greater embolic effect
RAI: Amiodarone → 3-6 months (longest); levothyroxine → 3-4 weeks; methimazole → 2-5 days
MIBG: Antipsychotics → ~3-4 weeks (longest); labetalol → 10 days; TCA → 1-3 days
FDG PET: G-CSF → 2-4 weeks; chemotherapy → 2-3 weeks; radiotherapy → 2-3 months
Mo-99 breakthrough: ≤0.15 µCi Mo-99/mCi Tc-99m → lead container + dose calibrator
Al³⁺ breakthrough: ≤10 µg/mL → colorimetric test
Radiochemical purity (RCP): ≥90% for most Tc-99m kits → measured by TLC
TLC + acetone → measures free pertechnetate (migrates with the front)
TLC + saline → measures colloidal Tc (stays at the origin)
RCP = 100 - free TcO₄⁻ (%) - colloidal Tc (%)
Large joint (knee): Y-90 (penetration 11 mm)
Medium joint (shoulder, hip): Re-186 (penetration 3.6 mm)
Small joint (finger): Er-169 (penetration 1 mm)
Teff = (Tphys × Tbiol) / (Tphys + Tbiol)
Always shorter than both the physical and the biological half-life
The effective half-life is used in dose calculations (MIRD)
<10 nm → blood capillaries (10-100 nm → lymph nodes)
10-100 nm → sentinel lymph node (filtered sulphur colloid)
100-1000 nm → RES phagocytosis (sulphur colloid)
10-100 µm → capillary blockade (MAA)
20-60 µm → microsphere embolisation (Y-90 SIR-Spheres)
Pertechnetate → trapping only (entry via NIS, no organification)
Iodine (I-123, I-131) → trapping + organification
Discordant nodule: hot on Tc-99m, cold on iodine → malignancy risk → biopsy
NETTER-1 trial → PFS benefit
Dose: 7.4 GBq × 4 cycles (8 weeks apart)
Renal protection: Amino acid infusion (lysine + arginine) → reduces tubular reabsorption
Dose-limiting organs: Kidneys and bone marrow
VISION trial → OS and PFS benefit
Dose: 7.4 GBq × 6 cycles (6 weeks apart)
Patient selection: Positivity must be confirmed by PSMA PET
Dose-limiting: Salivary glands (xerostomia), kidneys, bone marrow
13. Endocrine System
Anti-Tg antibodies cause falsely low values in immunometric (IMA) Tg assays → Tg is always measured together with anti-Tg.
Thyrotoxicosis + low uptake: serum Tg is suppressed in thyrotoxicosis factitia and high in thyroiditis.
Perchlorate discharge test (I-123): >10% fall in uptake after perchlorate → organification defect (Pendred, TPO defect, Hashimoto).
~25% of MTC is hereditary (germline RET) → RET testing in every MTC; MEN2A: MTC + phaeo + HPT, MEN2B: MTC + phaeo + marfanoid habitus + mucosal neuromas (no HPT).
MIBG sensitivity is ~90% in phaeochromocytoma/neuroblastoma, ~50-70% in carcinoid and ~30% in MTC; there is normally no bone/bone marrow uptake → skeletal uptake favours metastasis.
1. NIS location: Basolateral membrane. NIS is expressed not only in the thyroid but also in the salivary glands, gastric mucosa, lactating breast and choroid plexus.
2. Pertechnetate vs iodine: Pertechnetate → trapping only (no organification). Iodine (I-123, I-131) → trapping + organification. Discordant nodule: hot on pertechnetate, cold on iodine → FNAB required.
3. Normal thyroid uptake values: 24 hours → 10-30%. 4. Hyperthyroidism + low uptake: Thyroiditis (subacute, silent, postpartum), exogenous hormone, iodine loading, struma ovarii.
5. Hyperthyroidism + high uptake: Graves (diffuse homogeneous), toxic MNG (heterogeneous), toxic adenoma (focal + suppressed surroundings).
6. Cold nodule: Malignancy risk 5-15% → FNAB indicated. 85-95% of cold nodules are benign. 7. Wolff-Chaikoff: High iodine → inhibition of organification → hypothyroidism (protective). Jod-Basedow: high iodine → hyperthyroidism in autonomous tissue (pathological).
8. Before RAI therapy: TSH target >30 mIU/L (hormone withdrawal or rhTSH), low-iodine diet for 1-2 weeks, mandatory pregnancy test, iodine-containing drugs stopped.
9. Stunning: Diagnostic I-131 → NIS expression falls → treatment efficacy falls. Prevention: use I-123, low-dose I-131 (≤3 mCi), give therapy within ≤72 hours.
10. Differentiated thyroid cancer: Papillary (80-85%) and follicular (10-15%) → RAI-avid. Medullary → not RAI-avid (C cell, no NIS). Anaplastic → not RAI-avid (dedifferentiated).
11. Post-therapy WBS: More sensitive than diagnostic WBS → additional lesions in 10-26% of patients. 12. Dosimetric therapy limits: Bone marrow ≤200 cGy, lung retention <80 mCi at 48 hours. 13. Thyroglobulin (Tg): Tumour marker after total thyroidectomy + RAI. Anti-Tg antibodies interfere with Tg measurement.
Anti-Tg antibodies cause falsely low values in immunometric (IMA) Tg assays → Tg is always measured together with anti-Tg.
Thyrotoxicosis + low uptake: serum Tg is suppressed in thyrotoxicosis factitia and high in thyroiditis.
Perchlorate discharge test (I-123): >10% fall in uptake after perchlorate → organification defect (Pendred, TPO defect, Hashimoto).
~25% of MTC is hereditary (germline RET) → RET testing in every MTC; MEN2A: MTC + phaeo + HPT, MEN2B: MTC + phaeo + marfanoid habitus + mucosal neuromas (no HPT).
14. Causes of PHPT: Single adenoma 80-85%, hyperplasia 10-15%, carcinoma 1-2%, double adenoma 2-5%. 15. Mechanism of MIBI retention: Lipophilic cationic complex → mitochondrial membrane potential. Oxyphil cells → rich in mitochondria → intense MIBI uptake.
16. Dual-phase principle: Slow washout in parathyroid adenoma → retention in the delayed phase. False negative: adenoma with rapid washout.
17. Subtraction technique: MIBI − pertechnetate (or I-123) = parathyroid. Superior to dual-phase in adenomas with rapid washout.
18. Ectopic parathyroid: Most commonly intrathymic. Inferior glands → 3rd pharyngeal pouch → migrate with the thymus. Superior glands → 4th pharyngeal pouch → more constant.
19. SPECT/CT: Superior to planar imaging → anatomical localisation + detection of ectopic glands. Many guidelines recommend routine SPECT/CT.
20. NP-59: Cholesterol analogue → adrenal cortex. Unilateral early uptake under dexamethasone → autonomous adenoma; absent bilateral uptake under dexamethasone is normal. No bilateral uptake in a non-suppressed study → suggests carcinoma (dedifferentiated). Its use has declined.
21. MIBG: Norepinephrine analogue → taken up by uptake-1 (NET). Thyroid blockade mandatory. Longest withdrawal: antipsychotics (~3-4 weeks; depot ~1 month). Physiological uptake: liver (most intense), heart, salivary glands, adrenal, bladder.
22. Phaeochromocytoma: 10% rule (currently: hereditary proportion up to 30-40%). MIBG sensitivity 85-95%. In paraganglioma Ga-68 DOTATATE > MIBG.
23. Neuroblastoma: The commonest extracranial solid tumour of childhood. MIBG sensitivity 88-93%. Curie score: semi-quantitative MIBG assessment. 8-10% MIBG-negative → FDG PET/CT.
24. OctreoScan: Binds SSTR2. Most intense physiological uptake: spleen. Low sensitivity in insulinoma. Replaced by Ga-68 DOTATATE.
25. Ga-68 DOTATATE PET/CT: Gold standard for NET staging. Sensitivity 92-97%. PRRT patient selection (Krenning ≥2). Theranostic pair: Ga-68 diagnosis → Lu-177 therapy.
26. Flip-flop phenomenon: Well-differentiated NET → DOTATATE (+), FDG (−). Poorly differentiated NET/NEC → DOTATATE (−), FDG (+).
27. NET grading: Grade 1: Ki-67 <3%. Grade 2: Ki-67 3-20%. Grade 3: Ki-67 >20%. 28. PRRT (Lu-177 DOTATATE): 7.4 GBq × 4 cycles, 8 weeks apart. Renal protection: amino acid infusion. NETTER-1 trial: PFS benefit in midgut NET.
29. Krenning score: Grade 0-4. For PRRT ≥Grade 2 (tumour ≥ liver). Grade 4 = equal to/greater than spleen.
30. Carcinoid syndrome: SSA (octreotide LAR) → symptom control + antiproliferative (PROMID, CLARINET trials).
MIBG sensitivity is ~90% in phaeochromocytoma/neuroblastoma, ~50-70% in carcinoid and ~ 30% in MTC; there is normally no bone/bone marrow uptake → skeletal uptake favours metastasis.
31. Pertechnetate: 74-111 MBq, peak uptake at ~20 min (2-5%), ~1 mSv; perchlorate test not possible. I-123: 7.4-14.8 MBq, normal 2-hour uptake 10-15%, ~1.2 mSv.
32. I-131 diagnostic WBS: 37-74 MBq after hormone withdrawal, 110-148 MBq with rhTSH (SNMMI/EANM 2022); not used diagnostically under 10 years of age except for thyroid cancer. SPECT/CT: remnant vs lymph node, lung vs rib, bowel vs pelvic bone.
33. I-124 PET/CT: 20-74 MBq orally; dosimetry at 4-24-48-72-96 hours; target dose ~300 Gy for remnant, 80-100 Gy for metastases.
34. Thyroid MIBI: Independent of TSH/NIS, requires viable cells. AIT-1 normal/increased, AIT-2 reduced/absent, AIT-3 mixed. Indeterminate nodule (>1 cm, EU-TIRADS 4-5, Bethesda III/IV): MIBI-negative → high NPV; WOind threshold −19%.
35. Parathyroid MIBI: 400-900 MBq; early 10-15 min, delayed 1.5-2.5 hours; MIBI SPECT/CT detection rate ~88%; main pitfall an MIBI-avid thyroid nodule.
36. Parathyroid PET: F-18 fluorocholine (choline kinase) → sensitivity 94%, PPV 97%, cure 93%; first choice in MEN, renal HPT, persistent/recurrent and normocalcaemic HPT. C-11 methionine (LAT1/2) less sensitive. Success in renal HPT = >50% fall in PTH.
37. NP-59 (EANM): 20 MBq, ~36 mSv/procedure; thyroid blockade mandatory; dexamethasone 4 mg/day from 1 week before; spironolactone stopped ≥6 weeks before; imaging on days 5 and 8.
38. MIBG (EANM): I-123 185-370 MBq (13 µSv/MBq), I-131 40-80 MBq (140 µSv/MBq); critical organ liver. Thyroid blockade for 2-3 days with I-123 and 5-10 days with I-131.
39. SSTR imaging: Tc-99m HYNIC-TOC (Tektrotyd®) first choice among gamma agents; In-111 pentetreotide ~12 mSv. DOTANOC has the broadest affinity (SSTR2/3/5); SUV values of different SSTR PET agents cannot be compared; critical organ for Ga-68 DOTATATE is the spleen.
40. Benign insulinoma: High GLP-1R, low SSTR2 → Ga-68 exendin-4 PET/CT (accuracy 94.4%); false positives nesidioblastosis, Brunner glands.
14. Cardiovascular System
Tl-201: Na⁺/K⁺-ATPase, first-pass extraction 85%, redistribution present, T½ = 73 hours, low energy (69-83 keV)
Tc-99m MIBI: Mitochondrial membrane potential, first-pass extraction 60-65%, no redistribution, marked hepatic excretion
Tc-99m Tetrofosmin: Mitochondria, first-pass extraction 54%, faster hepatic clearance than MIBI, labelling at room temperature
Ranking (first-pass extraction): Tl-201 > N-13 ammonia > Rb-82 > MIBI > Tetrofosmin
Exercise is always preferred → target heart rate: (220 − age) × 0.85
Vasodilators: Adenosine (direct A2A, T½ 10 s), dipyridamole (indirect), regadenoson (selective A2A, bolus, most widely used)
For all vasodilators: Caffeine stopped 12-24 hours before (theophylline 48 hours); antidote = aminophylline
Tl-201: Na⁺/K⁺-ATPase, first-pass extraction 85%, redistribution present, T½ = 73 hours, low energy (69-83 keV)
Tc-99m MIBI: Mitochondrial membrane potential, first-pass extraction 60-65%, no redistribution, marked hepatic excretion
Tc-99m Tetrofosmin: Mitochondria, first-pass extraction 54%, faster hepatic clearance than MIBI, labelling at room temperature
Ranking (first-pass extraction): Tl-201 > N-13 ammonia > Rb-82 > MIBI > Tetrofosmin
Exercise is always preferred → target heart rate: (220 − age) × 0.85
Vasodilators: Adenosine (direct A2A, T½ 10 s), dipyridamole (indirect), regadenoson (selective A2A, bolus, most widely used)
For all vasodilators: Caffeine stopped 12-24 hours before (theophylline 48 hours); antidote = aminophylline
Asthma/COPD → vasodilators contraindicated → dobutamine (antidote: esmolol)
LBBB → vasodilator preferred (exercise/dobutamine → false septal defect)
Diaphragmatic attenuation: Male, inferior, fixed defect, normal wall motion → prone imaging
Breast attenuation: Female, anterior/anterolateral, fixed defect, normal wall motion
Gated SPECT: Attenuation artefact vs true defect → normal motion = artefact
TID: Severe multivessel / left main disease → high risk
Increased lung uptake (Tl-201): Severe LV dysfunction → high risk
Balanced 3-vessel disease: Normal-looking MPI → MBF/CFR measurement with PET
Reverse redistribution (defect becoming more conspicuous on the delayed image): Mostly reperfused infarction, not ischaemia
The LBBB false defect is confined to the septum and spares the apex; extension to the apex/anterior wall indicates true LAD ischaemia
Hibernation: Perfusion ↓ + FDG ↑ (mismatch) → benefits from revascularisation
Stunning: Normal perfusion + transiently impaired function → recovers spontaneously
Scar: Perfusion ↓ + FDG ↓ (match) → irreversible
FDG PET mismatch → gold standard for viability
Tl-201 reinjection: 40-50% of fixed defects show fill-in
Allman meta-analysis: In viable myocardium revascularisation reduces annual mortality from 16% to 3.2%; no difference without viable myocardium
Viability preparation: Glucose loading (the exact opposite of sarcoidosis preparation!)
The most reproducible method of LVEF measurement
Doxorubicin monitoring: Fall ≥10% + LVEF <50% → stop chemotherapy
If baseline LVEF <50%: fall ≥10% or LVEF ≤30% → stop; baseline ≤30% → do not start
Phase analysis: Dyskinesia/aneurysm ~180° opposite phase to the ventricle; WPW pre-excitation site early phase
Red cell labelling: In vitro >97% (best), in vivo 75-80% (lowest)
AF → gating degraded → reduced accuracy
Delayed H/M ≥1.6 → low risk → good prognosis (normal ≥~1.8-2.0)
Delayed H/M <1.6 → sympathetic denervation → poor prognosis, high arrhythmic risk
DLB → MIBG reduced; Alzheimer → MIBG normal
Parkinson → MIBG reduced (postganglionic); MSA → MIBG preserved (preganglionic)
Detects ATTR amyloidosis (AL not detected)
Perugini Grade 2-3 + negative monoclonal protein → ATTR diagnosis without biopsy
SPECT/CT → mandatory to exclude blood pool activity
Patient preparation: ≥12-18 hours fasting + high-fat/low-carbohydrate (suppress physiological uptake)
Focal/focal-on-diffuse FDG → pathological; diffuse homogeneous → inadequate preparation
Normal perfusion + focal FDG ↑ → early active inflammation
Used to monitor treatment response
Rb-82: Generator, T½ = 75 s, Na⁺/K⁺-ATPase, vasodilator stress mandatory, daily Sr-82 breakthrough test
N-13 ammonia: Cyclotron, T½ = 10 min, glutamine synthetase, exercise stress possible, best resolution
O-15 water: Cyclotron, T½ = 2 min, free diffusion, first-pass extraction 100%, gold standard for MBF, rare in clinical practice
CFR = Stress MBF / Rest MBF → normal ≥2.0 → <2.0 abnormal → <1.5 severely abnormal
Balanced 3-vessel disease → detected by MBF/CFR
SSS: Total stress score; SRS: total rest score; SDS = SSS − SRS (amount of ischaemia)
Normal MPI → annual cardiac event risk <1% (warranty period ~2 years)
Ischaemic myocardium ≥10% → revascularisation should be considered
17-segment model (AHA): LAD → anterior + anteroseptal + apex (largest territory)
Tl-201: ~4% reaches the myocardium; extraction preserved in acidosis/hypoxia, reduced in fibrosis; plateau at 2-2.5 × resting flow; 74-111 MBq (+37 MBq reinjection); breastfeeding interrupted for 48 hours
Tc-99m agents: Plateau at ~2 × resting flow; 1-day protocol stress 250-400 MBq + 3 times that for rest ≥3 hours later; breastfeeding not interrupted
Withdrawal: β-blocker/Ca antagonist/nitrate 48 hours, dipyridamole 72 hours, theophylline 48 hours, caffeine ≥12 (preferably 24) hours
Rate-pressure product >25,000 adequate, >30,000 excellent; target heart rate >85%
Normal MPI annual MACE ~1% (women ~0.3%, pharmacological stress ~2%); post-stress stunning: EF fall lasting >60 min
Reverse mismatch: LBBB, early revascularised MI, non-ischaemic CMP, diabetes → considered viable
FPRNA: Shunt (Qp/Qs), RV function, cardiac output; 555-1110 MBq
Cardiac MIBG: 15 min and 4 hours, LEHR; ADMIRE-HF 2-year events 15% (H/M ≥1.6) vs 37%; 80-90% reduction in Lewy body diseases; PD/DLB threshold ~1.77
Amyloidosis: score ≥2 at 3 hours + AL excluded → ATTR; marked uptake may occur in >20% of AL
Cardiac sarcoidosis: 24-hour high-fat/low-carbohydrate diet; CAD should be excluded by perfusion
15. Skeletal System
Agent: Tc-99m MDP/HDP → chemisorption to hydroxyapatite
Most important determinant of uptake: Osteoblastic activity
Dose: 20-25 mCi, imaging 2-4 hours later
High sensitivity (~95%), low specificity
Critical organ: Bladder (renal excretion)
Commonest indication: Screening for bone metastases
Phase 1: Perfusion (flow) → arterial blood flow
Agent: Tc-99m MDP/HDP → chemisorption to hydroxyapatite
Most important determinant of uptake: Osteoblastic activity
Dose: 20-25 mCi, imaging 2-4 hours later
High sensitivity (~95%), low specificity
Critical organ: Bladder (renal excretion)
Commonest indication: Screening for bone metastases
Phase 1: Perfusion (flow) → arterial blood flow
Phase 2: Blood pool → soft tissue hyperaemia
Phase 3: Delayed (bone) → osteoblastic activity
Osteomyelitis: Focally increased in all three phases
Cellulitis: Phases 1-2 diffusely increased, phase 3 normal
Low specificity in the diabetic foot → labelled leucocytes + bone marrow preferred
Acute osteomyelitis: Bone scintigraphy positive at 24-72 hours, radiography only at 10-14 days; a continued rise in the lesion/bone ratio at 24 hours favours osteomyelitis
Mechanism: Exchange with OH⁻ → fluorapatite
First-pass extraction: 100%
Compared with Tc-99m MDP: Higher sensitivity, better resolution, faster (45-60 min)
Disadvantage: Cost, access
Metastatic: Asymmetric, heterogeneous → prostate, breast cancer
Metabolic: Symmetric, homogeneous → HPT, renal osteodystrophy, osteomalacia
Common feature: Kidneys not visualised
"Beautiful bone scan" → may be a superscan → check the kidneys!
Multiple myeloma (board classic → purely osteolytic)
Renal cell carcinoma, anaplastic thyroid cancer
Early AVN, after radiotherapy, metal prosthesis
In myeloma → use FDG PET/CT or low-dose whole-body CT
Free pertechnetate → thyroid, stomach, salivary glands (labelling failure)
Metastatic calcification → lung, stomach, kidney (hypercalcaemia)
Dystrophic calcification → MI, rhabdomyolysis, myositis ossificans
H (Honda) sign: Sacral insufficiency fracture
Doughnut pattern: AVN (late phase)
Expanded bone + intense uptake: Paget disease
Periarticular increased uptake: CRPS (RSD)
Rosary bead: Osteomalacia (costochondral junctions)
Double density sign: Osteoid osteoma (intense nidus + surrounding reactive uptake)
Bilateral symmetric linear periosteal uptake along long bone cortices ("tram-track"): hypertrophic pulmonary osteoarthropathy (bronchogenic carcinoma)
Early phase: Cold lesion (blood flow interrupted)
Late phase: Increased uptake or doughnut pattern (reparative)
Gold standard: MRI
Commonest location: Femoral head
Normal postoperative uptake: Uncemented → 2 years, cemented → 6-12 months
Loosening vs infection → bone scintigraphy alone cannot distinguish them
Gold standard: Labelled leucocyte + bone marrow scintigraphy
Incongruent pattern → infection; congruent → no infection
Paradoxical worsening 2-3 months after treatment
Sign of good prognosis (response to treatment)
Improvement at 6 months → flare; continued worsening → progression
Positive 2-4 weeks before radiography
Spondylolysis → evaluate with SPECT/CT
Bone scintigraphy after trauma: positive 24-72 hours later (may be delayed in the elderly)
MRI → positive immediately → preferred for urgent evaluation
Shin splints: Longitudinal superficial uptake along the posteromedial tibial cortex, only the delayed phase positive (in stress fracture: focal fusiform, all three phases positive)
Bone scintigraphy + radiography → complementary
Bone scintigraphy → better for rib fractures; classic metaphyseal lesion and skull fracture → radiography better
Radiography → better for skull fractures
Most frequently involved bone: Pelvis
Complication: Osteosarcoma (less than 1%)
Bone scintigraphy → assessment of disease extent and activity
Treatment response: Reduced uptake after bisphosphonates
A photopenic area or intense FDG uptake in Paget disease → think of sarcomatous transformation
Vertebral body → high probability of metastasis
Facet joint / posterior elements → high probability of degenerative change
Disc space + both adjacent vertebrae → discitis-osteomyelitis
Bisphosphonate kinetics: at 4 hours ~60% skeleton, ~34% urine, ~6% circulation; maximal bone accumulation at 1 hour; adult 300-740 MBq, 4.9 µSv/MBq (3-4 mSv)
Soft tissue ↑: Renal failure, dehydration, failed labelling, short wait; ↓: superscan, very long wait; commonest artefact: urinary contamination
NaF: 50% in bone, ~30% in red cells; 185-370 MBq, 17 µSv/MBq, critical organ bladder; axial 30-45 min, extremities 90-120 min; valuable in ESRD and morbid obesity
DXA: T ≤ −2.5 osteoporosis, −1.1/−2.4 low bone mass; premenopausal/men <50 → Z score (≤ −2.0); forearm → non-dominant radius 33%; patient dose 1-10 µSv
16. Urinary System
Tc-99m MAG3: Tubular secretion (~95-98%; protein binding ~90%), extraction fraction ~ 40-50%, measures ERPF, the preferred agent
Tc-99m DTPA: Glomerular filtration, extraction fraction ~20%, measures GFR
Tc-99m DMSA: Cortical retention, static imaging, pyelonephritis/scar, differential function (most accurate)
MAG3 → good images even with low function → general preference
DTPA → when GFR measurement is required
Phase 1: Vascular (0-30 s) → perfusion
Phase 2: Parenchymal (1-5 min) → uptake → Tmax occurs here → differential function is calculated here
Tc-99m MAG3: Tubular secretion (~95-98%; protein binding ~90%), extraction fraction ~40-50%, measures ERPF, preferred agent
Tc-99m DTPA: Glomerular filtration, extraction fraction ~20%, measures GFR
Tc-99m DMSA: Cortical retention, static imaging, pyelonephritis/scar, differential function (most accurate)
MAG3 → good images even with low function → general preference
DTPA → when GFR measurement is needed
Phase 1: Vascular (0-30 s) → perfusion
Phase 2: Parenchymal (1-5 min) → uptake → Tmax occurs here → differential function is calculated here
Phase 3: Excretion (5+ min) → drainage → T½ is calculated here
Normal Tmax: 3-5 min (MAG3), Normal T½: <10 min
T½ <10 min → non-obstructive
T½ 10-20 min → equivocal
T½ > 20 min → obstructive
Commonest cause of false positives: Dehydration
In a very dilated system: F-15 protocol preferred (reduces the reservoir effect)
Furosemide dose: Adult 40 mg IV, paediatric 1 mg/kg
Commonest level of obstruction: UPJ in children, UVJ in adults (mostly stones)
Sawtooth fluctuation in the drainage phase → VUR during renography (not a sign of obstruction)
Principle: ACE inhibition → efferent arteriolar dilatation → fall in GFR → asymmetry
Most sensitive criterion: Prolonged Tmax
ACE inhibitors should be stopped 3-5 days before the study
False negative in bilateral stenosis (symmetric deterioration → no asymmetry)
Positivity thresholds (MAG3): Prolongation of Tmax by ≥2 min, rise in the 20-min/peak ratio of ≥0.15; with DTPA a fall in relative uptake
Use has declined today → CT/MR angiography more widely used
GFR gold standard: Inulin clearance (physiological), practical: Tc-99m DTPA
ERPF gold standard: PAH clearance, practical: Tc-99m MAG3
Normal GFR: 120 ± 25 mL/min
Normal ERPF: 600 ± 150 mL/min
Filtration fraction: GFR/RPF ≈ 20%
Gates method: Camera-based GFR → fast, gives differential GFR
Imaging: 2-4 hours after injection
Acute pyelonephritis: Focal reduced uptake, NO volume loss
Renal scar: Focal defect + volume loss (cortical thinning)
Most sensitive method for diagnosing acute pyelonephritis in children (with SPECT)
Most accurate method for measuring differential function
Pseudotumour (column of Bertin, dromedary hump) shows normal cortical uptake → distinguished from a true mass
Initial assessment: VCUG (anatomical detail, VUR grade, urethral pathology)
Follow-up: DRNC (low radiation, high sensitivity, continuous dynamic imaging)
Catheter-free method: IRNC (requires a cooperative patient, >3 years, voiding phase only)
DRNC radiation dose: ~1/100 of VCUG
Imaging: Anterior (pelvic location)
Preferred agent: Tc-99m MAG3
ATN vs Acute Rejection → the most important difference: Perfusion
ATN: Perfusion preserved, improvement on serial follow-up
Rejection: Perfusion reduced, deterioration on serial follow-up
Photopenic kidney (no perfusion + no uptake): Hyperacute rejection or renal artery thrombosis
Activity collection outside the bladder: Urine leak (urinoma)
A urinoma is photopenic early and accumulates activity over time; a lymphocele remains photopenic on delayed images too
ATN → common with deceased donors (cold ischaemia)
Chronic rejection → definitive diagnosis: Biopsy
"Which agent with low renal function?" → MAG3
"Which agent for GFR measurement?" → DTPA
"Most sensitive for diagnosing pyelonephritis?" → DMSA SPECT
"Preferred for VUR follow-up?" → DRNC
"Difference between transplant ATN and rejection?" → Perfusion (preserved in ATN)
"Principle of captopril renography?" → Efferent arteriolar dilatation → fall in GFR
"Limitation of captopril renography in bilateral stenosis?" → False negative
"Filtration fraction?" → 20% (GFR/RPF)
First-pass extraction: OIH ~80% > Tc-99m EC ~65% > MAG3 ~55% > DTPA ~20%
EANM activities: MAG3 75 MBq, DTPA 37-185 MBq, DMSA 70 MBq, DRNC 20 MBq
MAG3: 80-90% protein binding, ~10% hepatobiliary; its clearance is not reported as ERPF; probenecid is stopped
Differential function: Rutland-Patlak best; symmetry 50 ± 7.5%; C-shaped perirenal background ROI; µ = 0.14/cm
Cr-51 EDTA: Clearance ratio to inulin 0.85-1.01; ascites/oedema/GFR <30 → EANM: urine collection instead of plasma sampling (BNMS 2018: adapted plasma methods with late/24-hour samples)
DMSA: Acute defect is patchy and follows the contour; scar is triangular and distorts the contour; Fanconi, bicarbonate, mannitol reduce uptake
DRNC: Pertechnetate may be absorbed in an augmented bladder → false positive → use DTPA or colloid
Captopril: Dehydration/sodium depletion cause false positives; at creatinine <1.7 mg/dL sensitivity/specificity ~90%
17. Pulmonary System
Particle size: 10-90 μm (mean 20-40 μm)
Standard particle number: 200,000-700,000
Proportion of arterioles occluded: 0.1-0.3% → haemodynamically safe
Injection position: Supine (to reduce the effect of gravity)
Biological half-life: 2-9 hours
Particle number in pulmonary hypertension: reduce to 100,000-150,000
In right-to-left shunt: Reduce particle number (risk of cerebral embolisation)
Particle size: 10-90 μm (mean 20-40 μm)
Standard particle number: 200,000-700,000
Proportion of arterioles occluded: 0.1-0.3% → haemodynamically safe
Injection position: Supine (to reduce the effect of gravity)
Biological half-life: 2-9 hours
Particle number in pulmonary hypertension: reduce to 100,000-150,000
In right-to-left shunt: Reduce particle number (risk of cerebral embolisation)
In pregnancy: Reduce activity (1-2 mCi); the particle number does not go below 100,000
Egg allergy → NOT a contraindication (MAA is made from human albumin)
If blood is drawn into the syringe → clot → "hot spot" artefact
Xe-133: 81 keV, washout phase most important (air trapping), posterior projection only, ventilation must be performed FIRST
Tc-99m DTPA aerosol: 140 keV, 0.5-2 μm, clumping problem in COPD, all projections, most widely used
Technegas: 140 keV, FDA-approved (2023)
Kr-81m: 190 keV, 13 s half-life, simultaneous imaging with Tc-99m, very expensive
Mismatch = perfusion defect + normal ventilation → favours PE
Match = perfusion + ventilation defect in the same area → not PE (COPD, pneumonia)
Reverse mismatch = ventilation defect + normal perfusion → mucus plug, bronchial obstruction
Stripe sign = rim of perfusion at the periphery of a perfusion defect → low probability of PE
Complete loss of perfusion to one lung is rare in PE → central tumour/compression by a hilar mass (if matched on ventilation: central carcinoma, foreign body, Swyer-James)
Reversal of the perfusion gradient (upper zone > lower zone) → pulmonary venous hypertension (left heart failure, mitral stenosis)
High probability: ≥2 large segmental mismatches (probability of PE ~80-90%)
Intermediate: The most problematic category → high non-diagnostic rate
Low probability: Small defects, non-segmental defects, matched defects (probability of PE ~ 10-15%)
Triple match in a lower lobe: Probability of PE ~33% → intermediate
Normal: Probability of PE <5% → PE excluded
Triple match in an upper/middle lobe: Low probability of PE
Clinical probability (Wells score) and the V/Q result should be assessed together
PIOPED II very low probability (<10%): Non-segmental defect, 1-3 small segmental defects, single-segment triple match in the middle/upper zone, stripe sign, large effusion without other defects
V/Q is more sensitive than CTPA for CTEPH screening; a normal V/Q excludes CTEPH
Large: >75% of a segment
Moderate: 25-75% of a segment
Small: <25% of a segment
V/Q preferred: Contrast allergy, renal failure, pregnancy, young woman, normal chest radiograph
CTPA preferred: Abnormal chest radiograph (COPD), alternative diagnosis sought, haemodynamic instability
SPECT → intermediate rate falls from 30-40% to <5% (SNMMI/EANM 2026)
SPECT/CT → attenuation correction + anatomical correlation + alternative diagnosis
ppoFEV1 = Preop FEV1 × (1 − perfusion fraction of the lung to be resected)
ppoFEV1 >40% or >0.8 L → surgery generally safe
ppoFEV1 30-40% → increased risk, further assessment
ppoFEV1 <30% or <0.8 L → high risk, generally contraindicated
Right lung segment number: 10, Left lung: 8-9, Total: 18-19
Right-to-left shunt: With Tc-99m MAA → uptake in systemic organs → normal <5%
Systemic activity after MAA: Brain uptake → right-to-left shunt; thyroid/stomach (no brain) → free pertechnetate
Left-to-right shunt: First-pass radionuclide angiocardiography → Qp/Qs ratio
Qp/Qs = 1.0 → normal
Qp/Qs > 1 → left-to-right shunt
Qp/Qs < 1 → right-to-left shunt
Qp/Qs > 1.5 → haemodynamically significant → consider surgical correction
Pulmonary AVM → Osler-Weber-Rendu syndrome (HHT)
Hepatopulmonary syndrome → cirrhosis + intrapulmonary vascular dilatation
"Preferred test for suspected PE in a pregnant patient?" → V/Q scintigraphy (low breast dose)
"Best ventilation agent in COPD?" → Technegas
"V/Q order with Xe-133?" → Ventilation FIRST (low energy first)
"Agent allowing simultaneous V/Q?" → Kr-81m (190 keV)
"PIOPED high-probability criterion?" → ≥2 large segmental mismatches
"Stripe sign?" → Low probability of PE
"Triple match in a lower lobe?" → Probability of PE ~33% (intermediate)
"ppoFEV1 safety limit?" → >0.8 L or >40%
"Normal right-to-left shunt?" → <5%
"How is a left-to-right shunt assessed?" → First-pass angiocardiography, Qp/Qs
"Can a left-to-right shunt be assessed with MAA?" → NO
MAA: 40-120 MBq, 11 µSv/MBq, breastfeeding 12 hours; <100,000 particles (SNMMI/EANM 2026) or non-supine injection → irregular distribution
EANM PE criterion: ≥1 segment or ≥2 subsegment mismatch; V/Q SPECT ≥95% diagnostic, NPV ≥97%; with CT specificity 88% → 100%
Ventilation doses: Kr-81m lowest (27 nSv/MBq); Technegas 20-30 MBq (15 µSv/MBq); DTPA aerosol 900-1300 MBq in the nebuliser (SNMMI/EANM 2026)
DTPA aerosol clearance: Normal <2%/min; 2-5 times faster in smokers; increased in fibrosis, sarcoidosis, ARDS, PCP
Mucociliary clearance: Normal nasal ~6 mm/min, tracheobronchial ~4 mm/min; ~0.2 mm/min in PCD
18. Gastrointestinal System
Agent: Tc-99m pertechnetate (taken up via NIS)
Stimulation: Lemon juice (at 15-20 minutes)
Sjögren syndrome: Reduced uptake + absent/reduced secretion
Pertechnetate-avid tumour: Warthin tumour (hot nodule)
Commonest salivary gland tumour: Pleomorphic adenoma → does not take up pertechnetate (cold)
Agent: Tc-99m sulphur colloid (in liquid)
Normal transit time: <15 seconds (classical); EANM upper limit ≤30 seconds
Agent: Tc-99m pertechnetate (taken up via NIS)
Stimulation: Lemon juice (at 15-20 minutes)
Sjögren syndrome: Reduced uptake + absent/reduced secretion
Pertechnetate-avid tumour: Warthin tumour (hot nodule)
Commonest salivary gland tumour: Pleomorphic adenoma → does not take up pertechnetate (cold)
Agent: Tc-99m sulphur colloid (in liquid)
Normal transit time: <15 seconds (classical); EANM upper limit ≤30 seconds
Scleroderma: Retention in the lower 2/3 of the oesophagus (smooth muscle involvement)
Achalasia: Retention at the LOS
Agent: Tc-99m sulphur colloid (in acidic liquid/milk)
Lung activity on delayed images → pulmonary aspiration
The preferred non-invasive method in paediatric patients
Gold-standard method
Standard meal: Egg-white sandwich (Tc-99m sulphur colloid)
<30% retention at 1 hour → rapid emptying (dumping)
>10% retention at 4 hours → gastroparesis (Mild 11-20%, Moderate 21-35%, Severe >35%)
Solid food: Linear kinetics (lag phase + linear phase)
Liquid food: Exponential kinetics
Geometric mean: For attenuation correction (square root of anterior × posterior)
Blood glucose in a diabetic patient: ≤275 mg/dL
Drug withdrawal: Prokinetics, opioids, anticholinergics → 48-72 hours before
Truncal vagotomy: Liquids empty rapidly (loss of fundic relaxation), solids are delayed (impaired antral grinding)
Agent: Tc-99m pertechnetate IV → uptake by ectopic gastric mucosa
Rule of twos: 2%, 2 feet, 2 inches, 2 years, 2 types of mucosa, 2:1 M/F
Premedication: Cimetidine (H2 blocker) → blocks secretion → signal increases
Positive finding: Focal activity in the right lower quadrant → appears at the same time as the stomach
Sensitivity in children: 85-95%; in adults: 60-70%
Pancreatic mucosa → does not take up pertechnetate → scintigraphy negative
Agent: Tc-99m labelled red blood cells
Labelling efficiency: In-vivo 75-80%, In-vivtro 85-90%, In-vitro >95%
Detection threshold: 0.1-0.4 mL/min (angiography: 0.5-1.0 mL/min)
Localisation: The first focal activity to appear is the most reliable
Delayed imaging up to 24 hours → advantage in intermittent bleeding
Free pertechnetate → uptake in the stomach, thyroid, kidney → artefact
Gastric activity + thyroid/salivary glands seen → free pertechnetate; not seen → true gastric/upper GI bleeding
Agents: Mebrofenin/BrIDA (most common; preferred in hyperbilirubinaemia), DISIDA (sufficient at bilirubin <5 mg/dL)
Bilirubin >5 mg/dL → mebrofenin; >20 mg/dL → even mebrofenin may be inadequate
Acute cholecystitis: 60 min without gallbladder visualisation → morphine augmentation (0.04 mg/kg IV)
Mechanism of morphine: Contraction of the sphincter of Oddi → biliary pressure rises
Rim sign → gangrenous cholecystitis / perforation → emergency surgery
Morphine is given only after bowel activity (common bile duct patency) has been seen; the main cause of false negatives is acalculous cholecystitis
GBEF: Sincalide (CCK-8) 60 min infusion → normal ≥38%; <38% → dyskinesia
Neonatal jaundice: Phenobarbital 5 mg/kg/day for 5 days → distinguishes biliary atresia from hepatitis
Biliary atresia: NO passage into the bowel at 24 hours (not specific: severe neonatal hepatitis, Alagille, α1-antitrypsin deficiency); Kasai <60 days most successful
Bile leak: Focal accumulation of activity outside the bile ducts
Normal distribution: Liver 85-90%, Spleen 5-10%, Bone marrow 3-5%
Colloid shift → cirrhosis (splenic and bone marrow uptake increased)
FNH → takes up sulphur colloid (contains Kupffer cells)
Adenoma, metastasis, cyst, abscess → do not take up sulphur colloid
Budd-Chiari → increased caudate lobe uptake (direct IVC drainage)
Flow phase: Reduced/normal perfusion
Delayed phase: Increased uptake (more intense than the liver) → fill-in pattern
Sensitivity: >2 cm lesions 90-95%; at 1.5 cm low → MR preferred
Specificity: 95-100%
Malignant tumour: Increased in the flow phase, reduced in the delayed phase (the exact opposite)
Detects H. pylori urease activity
C-14: Radioactive → contraindicated in pregnancy; C-13: Non-radioactive → safe
PPI withdrawal: 2 weeks; Antibiotic/bismuth withdrawal: 4 weeks
Eradication check: 4 weeks after treatment
Sensitivity and specificity: >95%
Salivary gland: 37 MBq, maximum uptake at ~30 min; increased uptake + reduced secretion in sialadenosis; breastfeeding 12 hours
ETS: Normal transit ≤30 s; sensitivity 95%, specificity 96% in achalasia/scleroderma; manometry is the gold standard
GOR: First-line pH-metry/impedance; valuable for airway reflux in children; 15 s/frame, 1 hour
Gastric emptying: Omelette 18-37 MBq; normal ≤90% (1 h), ≤60% (2 h), ≤10% (4 h); < 30% at 1 hour rapid; Grade 1-3: 11-20% / 21-35% / >35%
Meckel's: 200 MBq; ranitidine preferred; NO thyroid blockade with perchlorate; sensitivity ~85% in children, ~60% in adults
GIBS: 550-1110 MBq; high success with transfusion ≥500 mL/24 hours; not performed for chronic occult bleeding
HIDA: Mebrofenin most common; 111-185 MBq; GBEF >40% normal (EANM); obesity/diabetes/CCB/OCP give falsely low GBEF; SOD criteria
Colonic transit: In-111 DTPA; ~70% excreted at 48 hours is normal
19. Neurology
HMPAO → trapping by glutathione, 30 min stable (without stabiliser), shows luxury perfusion
ECD → trapping by esterases, 6 hours stable, may not show luxury perfusion
Both cross the BBB → assessment of parenchymal perfusion
"Freezes" the perfusion at the moment of injection → snapshot property
Crossed cerebellar diaschisis: reduced perfusion/metabolism in the cerebellar hemisphere contralateral to a supratentorial infarct/tumour (cerebellum normal on CT/MR)
Acetazolamide (1 g IV) reserve test: an area with exhausted reserve falls relative to baseline; contraindications are sulphonamide allergy and stroke within the last 3 days
Most intense uptake: Cerebral cortex, basal ganglia, thalamus
HMPAO → trapping by glutathione, 30 min stable (without stabiliser), shows luxury perfusion
ECD → trapping by esterases, 6 hours stable, may not show luxury perfusion
Both cross the BBB → assessment of parenchymal perfusion
"Freezes" the perfusion at the moment of injection → snapshot property
Crossed cerebellar diaschisis: reduced perfusion/metabolism in the cerebellar hemisphere contralateral to a supratentorial infarct/tumour (cerebellum normal on CT/MR)
Acetazolamide (1 g IV) reserve test: an area with exhausted reserve falls relative to baseline; contraindications are sulphonamide allergy and stroke within the last 3 days
Most intense uptake: Cerebral cortex, basal ganglia, thalamus
Sedative → may be given after injection (should not be given before)
Blood glucose should be <150-200 mg/dL (high blood glucose reduces brain FDG uptake)
Alzheimer: Bilateral temporoparietal + posterior cingulate/precuneus (earliest) → motor, visual cortex and basal ganglia spared
FTD: Frontal + anterior temporal → frontal dominant
DLB: Temporoparietal + occipital → occipital involvement distinguishes it from Alzheimer
Vascular: Multiple, asymmetric, scattered
CBD: Asymmetric frontoparietal
PSP: Frontal + mesencephalon
3 FDA-approved agents: Florbetapir (Amyvid), Florbetaben (Neuraceq), Flutemetamol (Vizamyl)
Positive: Grey-white matter contrast lost → widespread cortical uptake
Negative: Grey-white matter contrast preserved → strong negative predictive value
Positive amyloid PET ≠ definite Alzheimer (asymptomatic positivity in 10-30% of the elderly)
Appropriate use: Unexplained cognitive impairment, atypical presentation, early-onset dementia
Flortaucipir (Tauvid, 2020) and florquinitau (Tauklarify, 2026) → FDA-approved tau PET agents
Tau burden is directly proportional to cognitive decline (unlike amyloid)
Reflects Braak staging in vivo
Off-target: Choroid plexus (most common), basal ganglia, MAO-B
I-123 Ioflupane → binds DAT → integrity of presynaptic dopaminergic neurons
Normal: Bilateral symmetric comma/crescent shape (caudate + putamen)
Early Parkinson disease: Putamen ↓, caudate preserved → "dot" shape
Abnormal: Parkinson disease, DLB, MSA, PSP, CBD
Normal: Essential tremor, drug-induced parkinsonism, psychogenic, Alzheimer
Bupropion → stopped 8 days before (phentermine ~14 days)
Levodopa, dopamine agonists, SSRIs → need not be stopped
Dopa-responsive dystonia (Segawa) → DaTscan normal (distinguishes it from early-onset PD)
Interictal SPECT: Hypoperfusion → sensitivity 40-50% (low)
Ictal SPECT: Hyperperfusion → sensitivity 90-95% → injection within the first 20-30 s is critical
SISCOM: Ictal − interictal SPECT → MRI co-registration → best localisation
Interictal FDG PET: Hypometabolism → sensitivity 80-90% (in TLE)
Ictal FDG PET: Practically not feasible
Tuberous sclerosis: tubers are hypometabolic on FDG; the epileptogenic tuber shows increased uptake on C-11 AMT PET
Preferred: Tc-99m HMPAO (or ECD) → crosses the BBB → parenchymal perfusion
Findings: Empty skull + hot nose
Tc-99m DTPA/pertechnetate → flow only → posterior fossa inadequate
Unlike EEG, perfusion scintigraphy is not affected by barbiturates/sedatives or hypothermia
Intrathecal In-111 DTPA → preferred (long T½ → imaging at 24-48-72 hours)
Normal: 2-4 hours basal cisterns → 12-24 hours convexities → no ventricular uptake
NPH: Early ventricular reflux + ventricular persistence + convexity block → benefits from a shunt
CSF leak: Pledget/plasma ratio >1.5 → positive
VP shunt patency: Tc-99m DTPA injected into the shunt reservoir → arrival in the peritoneal cavity is assessed
Perfusion SPECT: HMPAO/ECD 740 MBq; ECD 30-60 min, HMPAO 30-90 min after; phenytoin → cerebellar, benzodiazepines → frontal hypoperfusion
FDG brain: 150-250 MBq; MSA-P → putamen-thalamus ↓, MSA-C → cerebellum ↓, PSP → frontal + midbrain ↓, CBD → asymmetry
Amyloid PET: Florbetapir 370, flutemetamol 185, florbetaben 300 MBq; sensitivity ~94%, specificity ~97%; breastfeeding 12 hours
Tau PET: 1st generation flortaucipir (off-target); 2nd generation MK-6240, PI-2620; rarely appropriate in CU individuals
DaTscan: 150-250 MBq; perchlorate 200 mg; breastfeeding 4 days; distinguishes ET, cannot distinguish PD/MSA/PSP; binding declines with age
FDOPA: Carbidopa increases uptake ~2-fold; antiparkinsonian drugs stopped ≥12 hours
Cisternography: In-111 DTPA 20 MBq; reaches the convexity at ~24 hours; persistent ventricular reflux in NPH
20. Haematology and Lymphoma
FDG-avid lymphomas: HL, DLBCL, Burkitt, MCL, FL, peripheral T-cell → PET/CT standard
FDG-non-avid lymphomas: SLL/CLL, marginal zone (MALT), Waldenström → CT-based assessment
PET/CT in HL → has replaced bone marrow biopsy
In NHL (especially low grade) bone marrow biopsy may still be needed
PET/CT changes the stage in 10-30% (usually upstaging)
Splenic involvement (Lugano): diffuse uptake more intense than the liver, focal lesion or splenomegaly (>13 cm)
Rising SUV in follicular lymphoma → suspected transformation → biopsy
FDG-avid lymphomas: HL, DLBCL, Burkitt, MCL, FL, peripheral T-cell → PET/CT standard
FDG-non-avid lymphomas: SLL/CLL, marginal zone (MALT), Waldenström → CT-based assessment
PET/CT in HL → has replaced bone marrow biopsy
In NHL (especially low grade) bone marrow biopsy may still be needed
PET/CT changes the stage in 10-30% (usually upstaging)
Splenic involvement (Lugano): diffuse uptake more intense than the liver, focal lesion or splenomegaly (>13 cm)
Rising SUV in follicular lymphoma → suspected transformation → biopsy
Reference structures: Mediastinal blood pool and liver
Score 1: No uptake
Score 2: ≤ Mediastinum
Score 3: > Mediastinum, ≤ Liver
Score 4: > Liver (moderately)
Score 5: >> Liver and/or new lesion
Interim PET: 1-3 negative, 4-5 positive
End-of-treatment PET (Lugano): 1-3 negative (CMR), 4-5 positive
Modification of Ann Arbor → PET at the centre
Bulky "X" modifier removed → mass size reported in cm
CMR: Deauville 1, 2 or 3 + no new lesions
In FDG-non-avid lymphoma → CT-based response assessment
Interim PET: decision on treatment de-escalation/escalation in HL
End-of-treatment PET: ≥3 weeks after chemotherapy (preferably 6-8 weeks), 8-12 weeks after RT
PET positivity before autologous stem cell transplantation → post-transplant relapse/poor prognosis
Thymic hyperplasia (thymic rebound) → young patients, triangular, symmetric
Inflammation/granulation tissue
Infection
Sarcoid-like granulomatous reaction
Brown fat
High blood glucose → competitive inhibition
Small residual disease (5-7 mm)
Low-grade lymphoma
Early imaging after treatment
RCM: Cr-51 labelled red cells → binds to red cell haemoglobin
Plasma volume: I-125 labelled albumin (RISA)
Cr-51 elution: 1% per day → source of error in long studies
RCM increased → absolute erythrocytosis (PV, secondary)
RCM normal + Hct raised → relative erythrocytosis (Gaisböck syndrome)
Normal RCM: Men 25-35 mL/kg, women 20-30 mL/kg
Cr-51 labelled red cells → serial blood samples
Normal Cr-51 half-life: 25-35 days
Spleen/liver ratio >2:1 → splenic sequestration → splenectomy beneficial
Spleen/liver ratio <2:1 → hepatic/diffuse → no benefit expected from splenectomy
Heat-damaged Tc-99m red cells → spleen-specific
Heating: 49-50°C, 20 minutes (optimal)
>50°C → excessive damage → the liver also clears them
Indication: Accessory spleen, functional asplenia, ectopic splenic tissue
Tc-99m sulphur colloid → not spleen-specific (liver 85% dominant)
Anti-CD20 + Y-90 (pure beta emitter, T½ 64 hours)
No gamma emission → cannot be imaged
Rituximab given beforehand → clears normal B cells → increases delivery to the tumour
Dose: Plt ≥150K → 0.4 mCi/kg; Plt 100-149K → 0.3 mCi/kg; Plt <100K → contraindicated
Maximum dose: 32 mCi
Dose-limiting toxicity: Thrombocytopenia
Nadir: 7-9 weeks; recovery: ~12 weeks
Long-term risk: MDS/AML (2-5%)
HAMA (murine antibody): rapid blood clearance in subsequent antibody studies, false elevation in immunometric assays
I-131 Tositumomab (Bexxar) → withdrawn from the market in 2014
Tc-99m sulphur colloid → RES uptake → liver dominant (85%)
In-111 chloride → transferrin receptor → erythroid precursors → bone marrow-specific
Peripheral expansion → chronic anaemia, myeloproliferative disorder
Focal defect → metastasis, AVN, lymphoma infiltration
Extramedullary haematopoiesis → liver, spleen, paravertebral
FDG PET after G-CSF → diffuse bone marrow uptake → false positive → wait 2-4 weeks
Stage I: Single lymph node region (or single extranodal – IE)
Stage II: ≥2 regions on the same side of the diaphragm (or localised extranodal + adjacent LN – IIE)
Stage III: Both sides of the diaphragm (or above the diaphragm + spleen)
Stage IV: Disseminated extranodal organ involvement (bone marrow, liver parenchyma, lung)
A/B: B symptoms (fever >38°C, night sweats, >10% weight loss/6 months)
Body fluid volumes: Cr-51 red cells 0.5-1 MBq + I-125 HSA 0.1-0.2 MBq; outside ±25% of the theoretical value is abnormal; body/venous Hct 0.93
Platelet survival: In-111 oxinate; normal 8-10 days; splenic sequestration → splenectomy response ~80%
Heat-damaged red cells: 49.5°C, 20 min; 74-185 MBq; SPECT/CT + iterative reconstruction; not used to diagnose haemolysis
Zevalin: Rituximab on days 1 and 8, 11-14 MBq/kg (max ~1200 MBq); nadir 7-9 weeks (FDA and EANM); EU authorisation expired in 2024
21. Oncological PET/CT
FDG → entry into the cell via GLUT-1 → phosphorylation by hexokinase → cannot be dephosphorylated by glucose-6-phosphatase → metabolic trapping
F-18 half-life: 110 minutes, cyclotron production, positron emission, 511 keV annihilation photons
In obese patients SUVbw is artificially high → use SUVlbm (SUL)
Physiological uptake: brain (most intense), myocardium (variable), urinary tract (excretion), tonsils, GI tract
Brown fat: symmetric cervical-supraclavicular uptake → prevented with a warm environment + beta-blocker
Myocardial suppression: prolonged fasting (≥12-18 hours) + high-fat diet + heparin → cardiac sarcoidosis/endocarditis protocol
SPN: >8-10 mm nodule → PET indicated; SUVmax >2.5 suspicious for malignancy
FDG → entry into the cell via GLUT-1 → phosphorylation by hexokinase → cannot be dephosphorylated by glucose-6-phosphatase → metabolic trapping
F-18 half-life: 110 minutes, cyclotron production, positron emission, 511 keV annihilation photons
In obese patients SUVbw is artificially high → use SUVlbm (SUL)
Physiological uptake: brain (most intense), myocardium (variable), urinary tract (excretion), tonsils, GI tract
Brown fat: symmetric cervical-supraclavicular uptake → prevented with a warm environment + beta-blocker
Myocardial suppression: prolonged fasting (≥12-18 hours) + high-fat diet + heparin → cardiac sarcoidosis/endocarditis protocol
SPN: >8-10 mm nodule → PET indicated; SUVmax >2.5 suspicious for malignancy
Colorectal: strongest indication is detection of recurrence; mucinous type → false negative
Thyroid: high Tg + negative RAI → FDG PET/CT (flip-flop phenomenon → poor prognosis)
Testis: PET is useful for a residual mass >3 cm in seminoma; not reliable in non-seminoma (mature teratoma)
Prostate: low FDG sensitivity → PSMA PET/CT preferred
HCC: well-differentiated → takes up choline (not FDG); poorly differentiated → takes up FDG
Head and neck CUP: PET/CT can detect the primary focus in 25-30%
PET after RT: no earlier than 3 months (to let inflammation subside)
Incidental focal thyroid FDG uptake → malignancy risk ~30-35% → US ± FNAB; diffuse bilateral uptake → usually thyroiditis/Graves
Incidental focal colonic FDG uptake → colonoscopy (adenoma/carcinoma); diffuse/segmental → physiological, colitis or metformin
Negative PET/CT ~12 weeks after head and neck CRT → planned neck dissection can be avoided (PET-NECK)
Metabolic flare on days 7-10 after tamoxifen in ER+ breast cancer → not progression, a predictor of hormone response
Pilocytic astrocytoma (WHO grade 1) takes up FDG intensely → should not be mistaken for a high-grade tumour
RECIST 1.1: anatomical (CT), PR ≥30% decrease, PD ≥20% increase + 5 mm
PERCIST 1.0: metabolic (PET), PR/PD: ≥30% and ≥0.8 SUL unit change in SULpeak, parameter SULpeak
RECIST/PERCIST are not used in lymphoma → Lugano/Deauville is used
Most common: infection/inflammation (increased glycolysis in activated macrophages)
Talc pleurodesis → takes up FDG for years
G-CSF → diffuse bone marrow/splenic uptake → wait 2-4 weeks
After surgery → wait 6-8 weeks
Rebound thymic hyperplasia (young patients after chemotherapy)
Mnemonic BMLP-CHR: Bronchioloalveolar, Mucinous, Lobular breast, Prostate, Carcinoid, HCC (well diff.), Renal
Most common patient factor: hyperglycaemia
Technical: small lesion (<8 mm) → partial volume effect
Ga-68 PSMA → Lu-177 PSMA (prostate cancer)
Ga-68 DOTATATE → Lu-177 DOTATATE (NET)
I-123/I-131 MIBG → I-131 MIBG therapy (phaeochromocytoma, neuroblastoma)
FAPI: very low background, targets tumour stroma (CAF), not yet FDA approved
FES: oestrogen receptor, ER status in metastatic breast cancer (FDA approved 2020)
C-11 Methionine / F-18 FET: brain tumours → low background in the brain (unlike FDG)
F-18 Fluciclovine: prostate recurrence; use declining with PSMA
F-18 NaF: bone metastases, sensitivity superior to Tc-99m MDP
SUVmax: most widely used in clinical practice; simple but noise-sensitive
SULpeak: preferred in PERCIST
Patient factor that most affects SUV: blood glucose
Standardisation is critical for follow-up PETs: same scanner, same reconstruction, same uptake time
Patient preparation: ≥4-6 hours fasting, blood glucose <150-200 mg/dL, 60 min uptake time, warm/quiet environment
Greatest contribution of PET: atelectasis-tumour differentiation + detection of metabolically active lymph nodes
GTV definition methods: fixed SUV threshold, percentage threshold (40-50%), gradient-based, adaptive threshold → no consensus yet
4D-PET: respiratory gating → reduces motion artefact, useful for lesions at the lung bases and in the upper abdomen
FDG: glucose <11 mmol/L; wait ≥10 days after CT, >2 weeks after G-CSF, 2-3 months after RT, ≥6 weeks after surgery
PSMA: Ga-68 100-200 MBq; ganglia and benign bone lesions are false positives; PSMA-1007 hepatobiliary excretion
Fluciclovine: 370 MBq, imaging after 3-5 min; lytic > sclerotic uptake
FES: SUVmax <1.5 → no response to hormone therapy expected; fulvestrant is stopped ~28 weeks beforehand
Brain tumour: amino acid PET (FET/FDOPA/MET) superior to FDG; dynamic FET early peak → high grade
PentixaFor (CXCR4): myeloma, MCL, MZL; APA detection in primary aldosteronism
22. Sentinel Lymph Node and Lymphoscintigraphy
SLN = the first lymph node reached by lymphatic drainage from the primary tumour
SLN negative → distal nodes 95-98% negative → unnecessary radical dissection is avoided
Popularised the concept: Donald Morton (melanoma), Armando Giuliano (breast)
Small particle → fast transport + low retention
Large particle → slow transport + high retention
Ideal range: 10-100 nm
Tc-99m Tilmanocept (Lymphoseek): specific binding to the mannose receptor (CD206) → receptor-based (not passive filtration) → fast transport + high retention → FDA approved (2013)
SLN = the first lymph node reached by lymphatic drainage from the primary tumour
SLN negative → distal nodes 95-98% negative → unnecessary radical dissection is avoided
Popularised the concept: Donald Morton (melanoma), Armando Giuliano (breast)
Small particle → fast transport + low retention
Large particle → slow transport + high retention
Ideal range: 10-100 nm
Tc-99m Tilmanocept (Lymphoseek): specific binding to the mannose receptor (CD206) → receptor-based (not passive filtration) → fast transport + high retention → FDA approved (2013)
USA: Tc-99m sulphur colloid (filtered); Europe: Tc-99m nanocolloid
Tc-99m HSA is not a colloid → shows lymphatic channels, not retained in the SLN
Breast: peritumoral, subareolar (all quadrants drain to the subareolar plexus), intradermal
Intratumoral injection is not recommended → may be trapped within the tumour
Melanoma: intradermal, at 2-4 points around the lesion/scar
Isosulfan blue: anaphylaxis 1-2%
Pulse oximetry artefact → SpO2 artificially low (not true hypoxia)
Methylene blue + SSRI → serotonin syndrome (MAOI effect)
Change in urine colour (transient, blue-green)
ACOSOG Z0011: early breast Ca, cN0, 1-2 positive SLNs → ALND not needed (when breast-conserving surgery + RT is planned)
MSLT-II: SLN-positive melanoma → CLND vs observation → no difference in survival → US surveillance sufficient instead of CLND
Breslow thickness ≥0.8 mm (or <0.8 mm + adverse prognostic factors)
SLN status → strongest prognostic factor
Lymphoscintigraphy is critical in truncal melanoma → drainage pattern unpredictable (30-40% unexpected drainage)
SPECT/CT very useful in head and neck melanoma (complex anatomy)
SLN positivity rises with Breslow: <1 mm ~5%, 1-4 mm ~15-25%, >4 mm ~30-40%
An interval (in-transit) node (e.g. popliteal, epitrochlear) is also accepted as an SLN and removed
10% rule (SLN): ≥10% of the highest ex vivo count → accepted as SLN
20% rule (parathyroid): ex vivo count more than ≥20% of background → parathyroid tissue
Do not confuse these two rules!
For SLNs close to the injection site → injection-site activity masks the SLN
Most common: in breast cancer when the tumour is close to the axilla
Solution: SPECT/CT, lead shield, delayed imaging, probe approach from a different angle
Most specific finding: dermal backflow
Liver uptake = normal lymphatic function (lymph → venous system → hepatic RES)
Absence of liver uptake = severe lymphatic insufficiency
Primary lymphoedema: aplasia (no channels), hypoplasia (few/thin channels), hyperplasia (dilated/tortuous – rare)
Most common cause of secondary lymphoedema: surgery + RT; most common worldwide: filariasis
ROLL: localisation of a non-palpable breast lesion (intratumoral Tc-99m + gamma probe)
SNOLL: ROLL + SLN biopsy in a single session
RSL: localisation with an I-125 seed (low energy 27-35 keV, half-life 59.4 days)
Radioguided parathyroidectomy: Tc-99m MIBI + gamma probe → minimally invasive surgery
NaI(Tl): high sensitivity, widespread, affected by moisture
CsI(Tl): compact, robust
CZT: excellent energy resolution, works at room temperature, compact, expensive
Scintillation probes superior at high energy (I-131, 511 keV); semiconductor probes compact, better energy resolution
Vulvar cancer: early stage, bilateral inguinofemoral SLN
Cervical cancer: early stage, cervical injection
Merkel cell carcinoma: aggressive; SLN recommended for staging
Endometrial cancer: cervical injection with ICG, fluorescence in robotic surgery
Oral cavity SCC: early stage, being investigated as an alternative to elective neck dissection
Colloid sizes: nanocolloid 5-80 nm, rhenium sulphide 50-200 nm, tilmanocept ~7 nm (CD206)
Strongest SLN criterion is the lymphatic channel; the hottest node is not always the SLN; SPECT/CT mandatory in OSCC
In pregnancy a one-day protocol with 10-15 MBq; ~1.2 µSv/MBq for small colloids
Semi-quantitative lymphoscintigraphy: 37-50 MBq, 15 min treadmill; normal inguinal uptake >14% (Co-57) / >9% (BMI)
23. Paediatric Nuclear Medicine
EANM Dosage Card or North American Consensus Guidelines → standard references
3 kg → multiplier 1 (baseline activity), 68 kg → multiplier 14 (adult dose)
Do not go below the minimum dose → inadequate image → repeat study → more radiation
Giving the adult dose directly is never acceptable
Webster and Clark rules are historical and not recommended in current practice
DMSA: most sensitive method for acute pyelonephritis (90-95%), imaging after 2-4 hours
Acute pyelonephritis → swelling; renal scar → volume loss, contour retraction → follow-up DMSA after 6 months to differentiate
EANM Dosage Card or North American Consensus Guidelines → standard references
3 kg → multiplier 1 (baseline activity), 68 kg → multiplier 14 (adult dose)
Do not go below the minimum dose → inadequate image → repeat study → more radiation
Giving the adult dose directly is never acceptable
Webster and Clark rules are historical and not recommended in current practice
DMSA: most sensitive method for acute pyelonephritis (90-95%), imaging after 2-4 hours
Acute pyelonephritis → swelling; renal scar → volume loss, contour retraction → follow-up DMSA after 6 months to differentiate
MAG3: preferred for paediatric diuretic renography → tubular secretion → good images even at low GFR
DTPA is inadequate in neonates (low GFR)
Diuretic renography T½: <10 min normal, 10-20 min indeterminate, >20 min obstruction
Bladder catheter → prevents the back-pressure effect (pseudo-obstruction)
In neonates wait 4-6 weeks (renal maturation)
Initial assessment → VCUG (anatomical detail, grading, urethral assessment)
Follow-up → DRC (50-100 times lower radiation dose)
Indirect cystography → no catheter needed, in toilet-trained children
Drugs that reduce MIBG uptake: tricyclic antidepressants, cocaine, amphetamine (uptake-1 inhibition); reserpine (inhibition of vesicular storage); labetalol (uptake-1 inhibition); phenylephrine, pseudoephedrine (competitive inhibition)
The most common extracranial solid tumour of childhood
Neural crest origin, most often the adrenal medulla
Diagnostic MIBG → I-123 preferred (low energy, SPECT possible, low dose)
90-95% of neuroblastomas are MIBG-positive
MIBG-negative → FDG PET/CT or F-18 DOPA PET
Thyroid blockade is mandatory (KI or Lugol, start 24 hours before)
Stage 4S (MS): <12 months (<18 months in INRGSS), localised + limited metastases → spontaneous regression may occur
Curie score: 9 skeletal segments + soft tissue → each 0-3 → max. 30 → response monitoring → ≤2 good prognosis
MYCN amplification → poor prognosis
Growth plates → bilateral symmetric intense uptake = normal
Asymmetry → pathology (infection, trauma, tumour)
Child abuse (NAI): skeletal survey (radiography) primary + bone scintigraphy complementary
Disadvantage of bone scintigraphy: low sensitivity for skull fracture and classic metaphyseal lesion (CML)
Legg-Calvé-Perthes: early stage → cold lesion in the femoral head (avascular phase)
Neonatal osteomyelitis: may be a photopenic (cold) lesion → beware false negative!
Ewing sarcoma → diaphysis, osteosarcoma → metaphysis
Toddler's fracture (1-3 years): radiography often negative; on bone scintigraphy faint diffuse or oblique linear uptake along the tibia
Langerhans cell histiocytosis: lesions may be normal/cold on bone scintigraphy → radiographic skeletal survey is the mainstay; FDG PET/CT more sensitive
Perthes prognosis (Conway): early activity in the lateral column is good; neovascularisation from the base of the femoral head indicates poor prognosis
Tamponade in hip effusion (septic arthritis/transient synovitis) → reduced uptake in the femoral head in all phases → urgent decompression
Ewing sarcoma: FDG PET/CT more sensitive than bone scintigraphy for bone/bone marrow metastases
Meckel scintigraphy: Tc-99m pertechnetate → uptake in ectopic gastric mucosa
– Cimetidine → most commonly used sensitivity enhancer (inhibits secretion into the lumen)
– Sensitivity in children 85-95%
– Focal uptake simultaneous with the stomach → diagnostic
– No gastric mucosa → false negative
GER scintigraphy: lung activity on delayed images → pulmonary aspiration (most important finding)
– Also detects non-acid reflux (advantage over the pH probe)
Image Gently (2008) → campaign to reduce radiation dose in paediatric imaging
Go With the Guidelines → Image Gently + SNMMI nuclear medicine campaign
Increased risk in children: high cell division rate + long life expectancy + small body size
Feed-and-sleep technique → alternative to sedation in infants <1 year
Breastfeeding interruption: Tc-99m → most ≤4 hours (pertechnetate/MAA 12 h), I-123 NaI → 3-4 days, I-131 → stop completely
EANM dosage card: paediatric dose = baseline activity × multiplier; 3 kg → 1, 30 kg → 6.86, ≥68 kg → 14
Paediatric minimum activities: pertechnetate (thyroid) 10, MAG3 15, DMSA 18.5, DTPA/HIDA/Meckel/RBC 20, FDG 26, I-123 MIBG 37, bone 40, brain perfusion 100 MBq
I-123 MIBG thyroid blockade 2-3 days; diagnostic I-131 MIBG 5-10 days
24. Infection and Inflammation
Uptake mechanism: multiple → transferrin, lactoferrin, siderophores (bacteria-specific), leucocyte uptake
Half-life: 78.3 hours, gamma energies: 93, 185, 300, 394 keV
Imaging: 48-72 hours after injection, medium-energy collimator
Normal biodistribution: liver > spleen > bone marrow + kidney (early) + bowel (late)
Sarcoidosis patterns: Panda (parotid + lacrimal) + Lambda (bilateral hilar + right paratracheal) → together highly specific
Today replaced by FDG PET/CT for many indications
In-111 oxine: NO kidney/bladder uptake, NO bowel uptake (up to 24 hours) → preferred for abdominal infection
Uptake mechanism: multiple → transferrin, lactoferrin, siderophores (bacteria-specific), leucocyte uptake
Half-life: 78.3 hours, gamma energies: 93, 185, 300, 394 keV
Imaging: 48-72 hours after injection, medium-energy collimator
Normal biodistribution: liver > spleen > bone marrow + kidney (early) + bowel (late)
Sarcoidosis patterns: Panda (parotid + lacrimal) + Lambda (bilateral hilar + right paratracheal) → together highly specific
Today replaced by FDG PET/CT for many indications
In-111 oxine: NO kidney/bladder uptake, NO bowel uptake (up to 24 hours) → preferred for abdominal infection
Tc-99m HMPAO: kidney/bladder uptake PRESENT, bowel uptake PRESENT → better image quality, same-day result
Dual isotope (In-111 leucocytes + Tc-99m sulphur colloid): discordant = infection, concordant = bone marrow
Unreliable in spinal osteomyelitis → false negative → FDG PET/CT is preferred
Virgin bone: three-phase bone scintigraphy (first step) → if positive, labelled leucocytes
Complicated (prosthesis, fracture, Charcot): labelled leucocytes + bone marrow (dual isotope) → gold standard
Spinal: FDG PET/CT is preferred (labelled leucocytes unreliable)
Diabetic foot: dual isotope → over 90% accuracy → best for Charcot vs osteomyelitis
Strongest indication: FUO (50-70% diagnostic contribution)
Negative FDG PET/CT → high negative predictive value
Most important limitation: cannot distinguish infection from malignancy
In spinal osteomyelitis: sensitivity 96%, specificity 91%
FDG PET/CT → added to the Duke criteria as a major criterion (2015 ESC)
Myocardial suppression: ≥12-18 hours fasting + low-carbohydrate/high-fat diet + IV heparin
Limited role in native valves (physiological myocardial uptake)
Added value: whole-body scanning for septic emboli
FDG PET/CT → most valuable method (sensitivity 93-100%)
Focal uptake + perigraft gas → highly specific for infection
Diffuse mild uptake may be normal in the first 4-8 weeks postoperatively
Most specific pattern: perfusion defect + focal FDG uptake (mismatch)
Burned-out: perfusion defect + NO FDG uptake → scar
Myocardial suppression: same as the endocarditis protocol
Focal-on-diffuse uptake → may be active sarcoidosis BUT may be confused with inadequate suppression
FDG PET/CT → detects vascular inflammation early (prestenotic phase)
Grading: comparison with the liver → Grade 3 (vascular > liver) = active vasculitis
Vasculitis: diffuse smooth linear uptake; atherosclerosis: focal irregular uptake
Takayasu: young woman <40 years; giant cell arteritis: >50 years, temporal + large vessels
Ga-67: critical organ colon; marked bilateral renal uptake after 24 hours is pathological → acute interstitial nephritis (not expected in ATN)
With In-111-WBC the critical organ (highest dose) is the spleen
Normal chest radiograph + diffuse bilateral lung Ga-67 uptake → PCP; Kaposi sarcoma Ga-67-negative/Tl-201-positive
In IBD early imaging with Tc-99m HMPAO-WBC (30 min–2-3 hours) is essential → after that physiological bowel activity misleads
In acute osteomyelitis bone scintigraphy becomes positive at 24-72 hours; radiography at ~10-14 days
WBC: Tc-99m-WBC 185-370 MBq, In-111-WBC 10-18 MBq; positivity = uptake increasing over time; In-111-WBC preferred in the abdomen
Anti-granulocyte MoAb: besilesomab (NCA-95, HAMA → single administration), sulesomab (NCA-90, Fab', no HAMA)
Infection FDG: 175-350 MBq; SUV not validated; steroids deferred; no recommendation to stop antibiotics
25. Rare Applications
Radiopharmaceutical: Tc-99m pertechnetate/DTPA → drop into the lower conjunctival sac
Non-invasive, physiological assessment (contrast dacryocystography is invasive and anatomical)
Normal drainage: lacrimal sac (2-5 min) → nasolacrimal duct (5-10 min) → nasal cavity (10-15 min) → nasopharynx (15-20 min)
Superior to contrast methods for detecting functional epiphora
Complete obstruction: accumulation proximal to the obstruction, no passage distally
Tc-99m pertechnetate IV → NIS-mediated uptake
Acid stimulation (20 min) → normal: rapid washout
Radiopharmaceutical: Tc-99m pertechnetate/DTPA → drop into the lower conjunctival sac
Non-invasive, physiological assessment (contrast dacryocystography is invasive and anatomical)
Normal drainage: lacrimal sac (2-5 min) → nasolacrimal duct (5-10 min) → nasal cavity (10-15 min) → nasopharynx (15-20 min)
Superior to contrast methods for detecting functional epiphora
Complete obstruction: accumulation proximal to the obstruction, no passage distally
Tc-99m pertechnetate IV → NIS-mediated uptake
Acid stimulation (20 min) → normal: rapid washout
Sjögren: reduced uptake + delayed/absent washout (Grade 1-4)
Sialolithiasis: normal/increased uptake + NO washout (duct blocked, gland intact)
Warthin tumour: TAKES UP pertechnetate ("hot" nodule) → oncocytic cells, rich in mitochondria
Pleomorphic adenoma: does NOT take up pertechnetate ("cold" nodule)
Sialadenitis after I-131: reduced uptake + reduced washout (dose-dependent)
Intraperitoneal injection of Tc-99m MAA
Shunt patent → MAA passes into the venous system → lung uptake
Shunt occluded → activity remains in the peritoneal cavity → NO lung uptake
If Tc-99m sulphur colloid is used → liver/spleen uptake with a patent shunt
Tc-99m pertechnetate IV → angiographic phase + static phase
Acute torsion (<6 hours): reduced flow + COLD area
Late torsion (>24 hours): central COLD + peripheral HALO (ring of increased activity) → testis cannot be salvaged
Epididymitis/orchitis: increased flow + HOT area → the exact opposite of torsion
– Hydrocele: photopenic area around the testis (fluid) + normal testicular activity
The bell clapper anomaly predisposes to torsion and is often bilateral
The halo pattern is not specific to late torsion: also seen in abscess, haematoma and necrotic tumour
Torsion of the appendix testis: scintigraphy normal or focally increased ('hot dot'); false-negative torsion: spontaneous/intermittent detorsion
Today largely replaced by colour Doppler US
Oral Co-57/Co-58 labelled vitamin B12 → 24-hour urinary excretion measured
Phase 1 low + Phase 2 normal (corrected by adding IF) → pernicious anaemia
Phase 1 and Phase 2 low (adding IF does not correct) → ileal disease (Crohn, resection)
Not used today → Co-57/Co-58 production stopped → serological tests (anti-IF Ab, methylmalonic acid) are used
Cr-51 → red cell mass measurement + red cell survival
Normal red cell lifespan: 120 days (Cr-51 T½ = 25-35 days)
Polycythaemia vera vs relative polycythaemia: Cr-51 red cell mass → increased in PV, normal in relative polycythaemia
Spleen/liver ratio >2:1 → splenic sequestration → splenectomy beneficial
I-125 albumin → plasma volume measurement
In-111 oxine → platelet survival (normal: 8-10 days)
Tc-99m DTPA → percutaneous injection into the shunt reservoir (Ommaya/Rickham)
Patent shunt: activity progresses along the shunt line to the peritoneal cavity
Occluded shunt: activity does not progress → the level of occlusion is determined
Localised focal collection at the distal tip (no free spread in the peritoneum) → CSF pseudocyst/loculation
Cimetidine (H2 blocker): inhibits pertechnetate secretion → retention in the gland increases → target/background ratio increases (started 48 hours before the study)
Pentagastrin: increases pertechnetate uptake by gastric mucosal cells
Glucagon: reduces bowel motility → reduces artefact
Oral Tc-99m sulphur colloid (before going to bed at night) → morning lung imaging
Activity in the lungs → evidence of aspiration
Especially in paediatric patients (recurrent pneumonia, chronic cough)
Dacryoscintigraphy → physiological (scintigraphy) vs anatomical (contrast) assessment
Salivagraphy → Sjögren vs sialolithiasis (reduced vs normal/increased uptake)
Warthin tumour (and oncocytoma) → salivary gland tumours that take up pertechnetate
LeVeen shunt → MAA IP → lung uptake if patent
Testicular scintigraphy → torsion COLD, epididymitis HOT
Schilling test → historical, not used today
Salivary gland scintigraphy: 37 MBq; parenchyma vs outflow; breastfeeding 12 hours
Shunt scintigraphy: subcutaneous injection mimics distal occlusion → vertex view
26. Radionuclide Therapy
Fixed dose in Graves: 10-15 mCi, in TMNG: 15-30 mCi
Calculated dose formula: 3 parameters → target dose (µCi/g), gland weight (g), 24-hour RAIU (%)
Antithyroid drugs: methimazole stopped 2-5 days before; PTU 2-8 weeks before with fixed activity ( 4-7 days with a dosimetric approach) (radioprotective effect)
Graves ophthalmopathy: mild active → I-131 can be given with steroid prophylaxis; moderate-severe active → I-131 should be avoided
Most important risk factor (worsening ophthalmopathy): smoking
Most common outcome: hypothyroidism (50-80%)
In toxic adenoma the surrounding tissue is spared → suppressed tissue does not take up iodine
Fixed dose in Graves: 10-15 mCi, in TMNG: 15-30 mCi
Calculated dose formula: 3 parameters → target dose (µCi/g), gland weight (g), 24-hour RAIU (%)
Antithyroid drugs: methimazole stopped 2-5 days before, PTU 2-8 weeks before with fixed activity ( 4-7 days with the dosimetric approach) (radioprotective effect)
Graves ophthalmopathy: mild active → I-131 can be given with steroid prophylaxis; moderate-severe active → avoid I-131
Most important risk factor (worsening ophthalmopathy): smoking
Most common outcome: hypothyroidism (50-80%)
In toxic adenoma the surrounding tissue is spared → suppressed tissue does not take up iodine
RAI in paediatric Graves: avoided under age 5; acceptable at age 5-10 if activity is <10 mCi (ATA 2016)
TSH stimulation: THW → TSH >30 mIU/L or rhTSH (Thyrogen) 0.9 mg IM × 2 days
Stunning effect: diagnostic I-131 (>3 mCi) → reduces NIS expression → use I-123 or low-dose I-131 (≤3 mCi)
Low-risk ablation: 30 mCi, high risk: 100-200 mCi
Post-therapy WBS: 5-7 days after treatment → more sensitive than the diagnostic scan
Most common side effect: sialadenitis; most serious late complication: secondary malignancy (AML) → cumulative >600 mCi
Flip-flop phenomenon: I-131 uptake ↓, FDG uptake ↑ → dedifferentiation
TENIS syndrome: high Tg + negative I-131 scan → FDG PET/CT indicated
RAI-refractory: tyrosine kinase inhibitors (lenvatinib, sorafenib)
ATA 2015 excellent response: suppressed Tg <0.2 or stimulated Tg <1 ng/mL + imaging negative
Age threshold 55 in AJCC 8 DTC staging: under 55 only stage I (M0) or II (M1)
Thyroid blockade mandatory (SSKI/potassium iodide)
Drugs that reduce MIBG uptake: tricyclic antidepressants, labetalol, reserpine, sympathomimetics
MIBG positivity in neuroblastoma: 90-95%
Most important dose-limiting toxicity: bone marrow suppression
NETTER-1: advanced midgut NET → marked superiority in PFS
Protocol: 7.4 GBq × 4 cycles, 8 weeks apart
Renal protection: lysine + arginine amino acid infusion → reduces reabsorption by 40-50%
Patient selection: Ga-68 DOTATATE PET/CT positive, well-differentiated (Grade 1-2)
Renal dose limit: cumulative ≤23 Gy
VISION: OS advantage of 4 months in mCRPC (15.3 vs 11.3 months, HR 0.62)
PSMAfore: rPFS 12.0 vs 5.6 months in taxane-naive mCRPC
Protocol: 7.4 GBq × 6 cycles, 6 weeks apart
Patient selection: PSMA PET/CT positive → PSMA-negative lesion = poor prognosis
Most common side effects: fatigue, xerostomia, nausea; most common serious (Grade ≥3) toxicity: bone marrow suppression
ALSYMPCA: OS advantage of 3.6 months in mCRPC with bone metastases (14.9 vs 11.3 months)
Alpha emitter → range 100 µm → acts only at the bone surface
Protocol: 55 kBq/kg × 6 cycles, 4 weeks apart
Contraindications: visceral metastases, combination with abiraterone (ERA-223 → fracture risk)
Response marker: decline in ALP
Tc-99m MAA shunt study mandatory → hepatopulmonary shunt >20% → contraindicated
Shunt <10% → full dose; 10-15% → reduce by 20%; 15-20% → reduce by 40%
Glass microspheres: high specific activity (2500 Bq), few microspheres, little embolisation
Resin microspheres: low specific activity (50 Bq), many microspheres, more embolisation
TACE contraindicated in portal vein thrombosis → Y-90 can be given (advantage)
Lung dose limit: ≤30 Gy per session, ≤50 Gy cumulative
Normal liver dose limit: healthy ≤70 Gy, cirrhotic ≤40 Gy
Sr-89: pure beta, T½ 50.5 days, Ca analogue, no imaging, response in 2-4 weeks
Sm-153: beta + gamma (103 keV), T½ 46.3 hours, phosphonate, imaging possible, response in 1 week
Myelosuppression more marked with Sr-89 (long T½)
Purely lytic lesions without uptake on bone scintigraphy (e.g. multiple myeloma) do not respond; shortest beta range in tissue is Sm-153 (~0.6 mm)
Anti-CD20 + Y-90 → B-cell NHL
Crossfire effect: beta range ~5 mm → also kills neighbouring cells
Dose: PLT ≥150K → 0.4 mCi/kg; PLT 100-149K → 0.3 mCi/kg; PLT <100K → contraindicated
Most important toxicity: delayed myelosuppression (nadir 7-9 weeks)
Large joint (knee): Y-90 (range 11 mm)
Medium joint (shoulder, hip): Re-186 (range 3.6 mm)
Small joint (finger): Er-169 (range 1 mm)
Immobilisation for 48-72 hours after injection → prevents extra-articular leakage
MIRD formula: D = Ã × S
I-131 bone marrow limit: ≤200 cGy (2 Gy)
I-131 lung retention: at 48 hours ≤80 mCi
Lu-177 DOTATATE renal limit: ≤23 Gy
Y-90 cirrhotic liver limit: ≤40 Gy
NRC release: <7 mR/hour at 1 metre OR residual activity <33 mCi
Avoid pregnancy after I-131: 6-12 months
Breastfeeding after I-131: must be stopped (permanently for that child)
Ra-223, Y-90, Lu-177: minimal external radiation risk → no special isolation needed
Benign thyroid: stop thiamazole 2-5 days and PTU 2-8 weeks before (4-7 days with the dosimetric approach); wait 6-8 weeks after iodinated contrast; adenoma 300-400 Gy, TMNG >150 Gy
Ra-223: for subsequent doses ANC ≥1.0 and PLT ≥50×10⁹/L; excretion mainly faecal
Sr-89: standard 150 MBq; GFR <30 mL/min → not given; calcium stopped 2 weeks before
Y-90 RE: tumour dose in HCC: glass ≥205 Gy, resin ≥120 Gy; Ho-166 scout ~250 MBq, tumour ≥60 Gy
Lu-177 PSMA: highest doses in lacrimal/salivary glands and kidney; Ac-225 PSMA: 100 kBq/kg, xerostomia
EANM optimisation levels: L1 (cohort) – L2 (patient-specific dosimetry) – L3 (absorbed-dose-based prescription)
27. Quality Control and Regulation
First daily test: energy peak check (peaking) → if the photopeak is wrong, everything is affected
Daily uniformity: intrinsic = without collimator + point source (5 × FOV); extrinsic = with collimator + flood source
Uniformity formula: IU = (Max − Min) / (Max + Min) × 100%
Acceptable integral uniformity: ≤3-5% (intrinsic), ≤5% (extrinsic)
Minimum counts: 3-5 million (daily), >30-100 million (annual high-count)
Weekly: spatial resolution and linearity with a bar phantom
COR test: every 3-6 months, acceptable error ≤0.5 pixel
First daily test: energy peak check (peaking) → if the photopeak is wrong, everything is affected
Daily uniformity: intrinsic = without collimator + point source (5 × FOV); extrinsic = with collimator + flood source
Uniformity formula: IU = (Max − Min) / (Max + Min) × 100%
Acceptable integral uniformity: ≤3-5% (intrinsic), ≤5% (extrinsic)
Minimum counts: 3-5 million (daily), >30-100 million (annual high-count)
Weekly: spatial resolution and linearity with a bar phantom
COR test: every 3-6 months, acceptable error ≤0.5 pixel
SPECT ring artefact → non-uniformity
SPECT doubling → COR error
NaI(Tl) energy resolution: 9-10% (at 140 keV)
A planar non-uniformity of ~1% can grow to ~20% in SPECT → correction map: ~30 million counts at 64×64, ~120 million at 128×128
Co-57 sheet source (versus a Tc-99m liquid phantom): no preparation, constant thickness, no bubble/poor-mixing artefacts, low staff dose
Multiple window spatial registration (MWSR): superimposition of window images for multi-peak nuclides such as Ga-67/In-111; blurring when faulty
Daily QC source: Ge-68 (T½ = 271 days, positron emitter)
PET spatial resolution: 4-6 mm (FWHM)
SUV accuracy: ±10% acceptable
NECR: Noise Equivalent Count Rate → determines the optimal activity range
Streak artefact on the sinogram → faulty detector block
Partial volume effect: becomes marked when lesion diameter is <2-3 × resolution
IEC body phantom: 6 spheres (10-37 mm) → contrast recovery assessment
Daily: constancy → Cs-137 → ±5%
Annual: accuracy → NIST-traceable → ±5%
Every 6 months or annually: linearity → decaying source → ±10%
At installation: geometry dependence
Accuracy, linearity and geometry tests are repeated after a major repair or relocation
Radionuclidic purity: gamma spectrometry → Mo-99 breakthrough: ≤0.15 µCi/mCi Tc-99m
Mo-99 test: lead container (6 mm Pb) → Tc-99m is absorbed, Mo-99 passes through
Radiochemical purity (RCP): TLC → ≥90% (most Tc-99m kits; FDG/Ga-68 ≥95%)
Free TcO₄⁻: ITLC-SG + acetone → TcO₄⁻ migrates to the front
Colloid (TcO₂): ITLC-SG + saline → TcO₂ remains at the origin
Uptake of free TcO₄⁻: thyroid, stomach, salivary glands
Uptake of TcO₂ (colloid): liver, spleen, bone marrow
Chemical purity: Al³⁺ ≤10 µg/mL (colorimetric test) → risk of flocculation in sulphur colloid
FDG: Kryptofix ≤50 µg/mL, RCP ≥95%, pH 4.5-8.5
MAA particle size: 10-90 µm, number: 200,000-700,000
Pulmonary HT / right-to-left shunt → number of MAA particles reduced (≤100,000)
ICRP 103 occupational dose: 20 mSv/year (5-year average), ≤50 mSv in a single year
NRC occupational dose: 50 mSv/year (5 rem/year) → different from ICRP!
Lens of the eye (ICRP 118): 20 mSv/year (previously 150 mSv/year → an important change)
Public dose limit: 1 mSv/year
Fetal dose in a pregnant worker: ICRP → ≤1 mSv; NRC → ≤5 mSv (0.5 rem)
Medical event: >20% deviation + organ dose >50 rem or effective dose >5 rem
NRC notification: 1 day by telephone + 15 days written report
ALARA: time, distance, shielding
Radiation area: at 30 cm >5 mrem/hour
High radiation area: at 30 cm >100 mrem/hour
Unrestricted area limit: 2 mrem/hour
DIS: 10 half-lives are allowed → activity falls to ~1/1000
Tc-99m DIS: ~60 hours; I-131 DIS: ~80 days; F-18 DIS: ~18 hours
After DIS: radioactive labels must be removed → disposed of as normal waste
Long-lived waste (T½ >120 days): DIS cannot be applied → licensed facility
Mixed waste: most difficult to dispose of → subject to both NRC and EPA regulations
Discharge to the sewer: ≤1 Ci in total per year
Transport labels: White-I (TI = 0, surface ≤0.5), Yellow-II (TI ≤1, surface ≤50), Yellow-III (TI ≤10, surface ≤200)
Wipe test limit: 200 dpm/100 cm²
Decontamination: no harsh scrubbing → skin integrity is broken → absorption increases.
Dose calibrator: action level 3%, tolerance limit 5%; linearity at intervals of ≥6 months; reference source T½ >5 years (Cs-137)
Mo-99 breakthrough: eluate purity test; first eluate, repeated after >14 days; European limit 0.1%
SPECT/CT alignment ≤5 mm; PET/CT alignment every 6 months; daily PET QC with a Ge-68 phantom or Lu-176 (LSO)
Probe: ~200 kBq Co-57 for daily constancy; EARL → quantitative harmonisation between centres
28. New Developments - Theranostics and Artificial Intelligence
Theranostics: "See it → Treat it" → diagnosis + treatment directed at the same molecular target
Theranostic pair: same ligand + different radionuclides (diagnostic + therapeutic)
The most important theranostic pairs:
NETTER-1: Lu-177 DOTATATE → midgut NET → PFS prolonged
VISION: Lu-177 PSMA-617 → mCRPC → OS and rPFS prolonged
Patient selection is critical: target expression must be confirmed by imaging
NET – Krenning score ≥2 → suitable for PRRT
Theranostics: "See it → Treat it" → diagnosis + treatment directed at the same molecular target
Theranostic pair: same ligand + different radionuclides (diagnostic + therapeutic)
The most important theranostic pairs:
– Ga-68 / Lu-177 DOTATATE → NET (somatostatin receptor)
– Ga-68 / Lu-177 PSMA-617 → mCRPC (prostate-specific membrane antigen)
– I-123 / I-131 → thyroid cancer (NIS) and MIBG (norepinephrine transporter)
– In-111 / Y-90 → radioimmunotherapy (CD20)
– Cu-64 / Cu-67 → new-generation theranostic pair
– Ga-68 / Ac-225 → alpha therapy (PSMA)
NETTER-1: Lu-177 DOTATATE → midgut NET → PFS prolonged
VISION: Lu-177 PSMA-617 → mCRPC → OS and rPFS prolonged
Patient selection is critical: target expression must be confirmed by imaging
NET – Krenning score ≥2 → suitable for PRRT
Prostate – PSMA PET positive + no discordant disease → suitable for PSMA therapy
Discordant disease: PSMA-negative / FDG-positive → poor prognosis, low response to PSMA therapy
Cumulative kidney dose limit: 23 Gy (PRRT)
Cumulative bone marrow dose limit: 2 Gy
Renal protection: amino acid infusion (lysine + arginine)
High LET (~80-100 keV/µm) → double-strand DNA breaks
Short range (50-80 µm) → minimal damage to surrounding tissue
OER ~1 → effective in hypoxic tumours too
Ac-225 PSMA: promising in mCRPC refractory to Lu-177
Ra-223: approved alpha therapy → osteoblastic bone metastases
Disadvantage: recoil effect of daughter radionuclides → detachment from the target
Target: FAP (Fibroblast Activation Protein) → cancer-associated fibroblasts
Most important advantage: low physiological background (brain, liver)
Superior to FDG: peritoneal carcinomatosis, brain tumours, HCC, gastric/colorectal cancer
No patient preparation required (no fasting or blood glucose control)
Not tumour-specific → also taken up in wound healing, fibrosis and inflammation
Therapeutic potential: Lu-177 FAPI, Ac-225 FAPI → at the research stage
Problem: short tumour retention → limited therapeutic efficacy
F-18 PSMA-1007: alternative to Ga-68 PSMA → longer T½, central distribution → disadvantage: bone false positives
Zr-89: T½ = 78.4 hours → immuno-PET → suited to antibody pharmacokinetics
Cu-64: T½ = 12.7 hours → both β⁺ and β⁻ → theranostics in a single radionuclide
Ga-68 Pentixafor: CXCR4-targeted → haematological malignancies
CNN: the most common deep learning architecture for image analysis
U-Net: medical image segmentation
Dose reduction: AI denoising of low-count images → 50-75% dose reduction
Radiomics: extracting quantitative features from images
1st order: histogram (mean, SD, skewness)
2nd order: texture analysis (GLCM, GLRLM)
Higher order: filter-based (wavelet, LoG)
Challenges: data quality, generalisability, explainability ("black box"), regulatory approval
uEXPLORER: axial FOV = 194 cm → the first total-body PET/CT
Biograph Vision Quadra: axial FOV = 106 cm
Conventional PET: axial FOV = 15-30 cm
Increase in sensitivity: ~40-fold (uEXPLORER)
Options for use: ultra-low dose OR ultra-fast OR ultra-high quality
Dynamic whole-body imaging: simultaneous kinetic analysis in all organs → dosimetry in a single session
SiPM: a semiconductor photon detector replacing the PMT
Timing resolution: ~200 ps (PMT: ~500 ps)
Energy resolution: ~9-11% (PMT: ~12-15%)
– Unaffected by the magnetic field → used in PET/MR
– Compact design → small size
TOF formula: Δx = c × Δt / 2
– 500 ps → 7.5 cm | 200 ps → 3 cm | 60 ps → 0.9 cm
– SNR gain ∝ √(D/Δx) → the TOF advantage is more marked in large patients
CZT: direct-conversion detector (gamma → electrical, no intermediate step)
Energy resolution: ~5-6% (NaI(Tl): ~9-10%)
Cardiac CZT-SPECT: 5-8-fold increase in sensitivity → 2-5 min acquisition, 50% dose reduction
– Dynamic SPECT → MBF measurement possible (PET-like)
– Insufficient stopping power at 511 keV → not used in PET
Crystal comparison: LYSO (most common in modern PET) > LSO > BGO (older) | NaI(Tl) → SPECT
Photon-counting CT: counts each photon individually → spectral information → material decomposition
Compton camera: collimator-free → potential for very high sensitivity → not yet in clinical use.
SSTR antagonists (JR11, LM3, LM4): less internalisation, higher contrast in the liver; haematotoxicity with JR11
GRPR: pan-tumour target (prostate, breast); highest physiological expression in the pancreas
Immuno-PET: checkpoint antibodies with Zr-89; F-18 AraG for T-cell activation; FAP-high CAF → immunosuppression
iNM: hybrid tracer ICG-Tc-99m-nanocolloid; SLN false negatives 1-14%
AI: radiomics has the advantage on small data; 'no free lunch' → several models; interpretability ≠ explainability
29. Biostatistics and Bioethics
2×2 table: the basis of all calculations → TP, FP, FN, TN
Sensitivity = TP / (TP + FN) → catching disease → priority in screening tests
Specificity = TN / (TN + FP) → recognising the healthy → priority in confirmatory tests
PPV = TP / (TP + FP) → prevalence-dependent → prevalence ↑ → PPV ↑
NPV = TN / (TN + FN) → prevalence-dependent → prevalence ↑ → NPV ↓
Sensitivity and specificity are INDEPENDENT of prevalence (intrinsic properties of the test)
SnNOut: high Sensitivity + Negative result → rule disease out
2×2 table: the basis of all calculations → TP, FP, FN, TN
Sensitivity = TP / (TP + FN) → catching disease → priority in screening tests
Specificity = TN / (TN + FP) → recognising the healthy → priority in confirmatory tests
PPV = TP / (TP + FP) → prevalence-dependent → prevalence ↑ → PPV ↑
NPV = TN / (TN + FN) → prevalence-dependent → prevalence ↑ → NPV ↓
Sensitivity and specificity are INDEPENDENT of prevalence (intrinsic properties of the test)
SnNOut: high Sensitivity + Negative result → rule disease out
SpPIn: high Specificity + Positive result → rule disease in
LR+ > 10: strong diagnostic evidence (rules disease in)
LR− < 0.1: strong diagnostic evidence (rules disease out)
LR is independent of prevalence → its advantage over PPV/NPV
Normal distribution: ±1 SD ~68%, ±1.96 SD 95%, ±3 SD ~99.7%; standard error of a proportion = √[p(1−p)/n]
Decision tree: square = decision node, circle = chance node, triangle = outcome; expected value = Σ probability × outcome
X axis: 1 − Specificity (FPR) | Y axis: Sensitivity (TPR)
AUC = 1.0: perfect | AUC = 0.5: chance level (diagonal) | AUC <0.5: worse than chance
Youden index: J = Sensitivity + Specificity − 1 → optimal threshold
DeLong test: statistical comparison of two AUCs
Strongest evidence: systematic review / meta-analysis > RCT > cohort > case-control > cross-sectional
RCT: can establish causality → randomisation balances confounders
Cohort: measures RR → unsuitable for rare diseases
Case-control: measures OR → most suitable for rare diseases → retrospective
Cross-sectional: measures prevalence → no temporal relationship can be established
Cumulative incidence (cohort) ≠ prevalence (cross-sectional, existing cases at a given time)
Phase 0 microdose (PK/biodistribution) → Phase I safety/dose → Phase II preliminary efficacy → Phase III comparative RCT → Phase IV post-marketing
ITT analysis: all randomised patients are analysed according to their initial groups
Meta-analysis: forest plot, I² (heterogeneity), funnel plot (publication bias)
I² > 75%: high heterogeneity
Type I error (α): saying there is a difference when there is none → false positive → usually 0.05
Type II error (β): saying there is no difference when there is one → false negative → usually 0.20
Power = 1 − β → usually ≥ 80% is targeted
Increases power: sample ↑, effect size ↑, α ↑, variance ↓
p value ≠ probability that H₀ is true (the most common misunderstanding!)
Statistical significance ≠ clinical significance → effect size and NNT should be assessed
NNT = 1/ARR → low NNT = effective treatment
Confidence level ↑ (95% → 99%) → interval widens; sample ↑ → interval narrows
Fisher's exact test: expected frequency < 5 → used instead of chi-square
Bonferroni correction: α / number of tests in multiple comparisons → very conservative
Formula: κ = (P₀ − Pₑ) / (1 − Pₑ)
κ = 1: perfect agreement | κ = 0: chance level | κ < 0: worse than chance
Landis & Koch: 0.41-0.60: moderate | 0.61-0.80: substantial | 0.81-1.00: almost perfect
Cohen's kappa: 2 observers, nominal data
Weighted kappa: ordinal data
Fleiss' kappa: >2 observers
ICC: agreement for continuous data
Bland-Altman: comparison of two measurement methods
Four basic principles (Beauchamp & Childress):
1. Autonomy → the patient's right to decide → informed consent 2. Beneficence → acting in the patient's interest 3. Non-maleficence → ALARA, justification 4. Justice → equal distribution of resources
The 3 ICRP principles: Justification + Optimisation (ALARA) + Dose limitation
ALARA → the reflection of non-maleficence in radiation protection
Nuremberg Code (1947): requirement for voluntary consent → after the Nazi experiments
Declaration of Helsinki (1964): ethics of research on human subjects → World Medical Association
Belmont Report (1979): respect for persons, beneficence, justice
5 elements: Disclosure, Understanding, Voluntariness, Decision-making capacity, Consent
Diagnostic nuclear medicine: verbal consent is usually sufficient
Therapeutic nuclear medicine (RAI, PRRT, PSMA): written consent is mandatory
Pregnancy: RAI therapy absolutely contraindicated → a pregnancy test before treatment is mandatory
Contraception after RAI: 6-12 months
Paediatric: Image Gently → dose reduction, EANM dosage card, strict justification
Breastfeeding: the interruption varies with the radiopharmaceutical → I-131: breastfeeding is stopped completely.
Data types: nominal (frequency/ratio), ordinal (median), quantitative (mean ± SD)
Correlation |r|: 0.4-0.6 moderate, 0.6-0.8 high, >0.8 very high; correlation ≠ agreement (Bland-Altman)
Survival: censored data, Kaplan-Meier, log-rank/Wald test