Part 1: L7, PET

Question 1

PET scan overview:

Answer 1

• Suing radiation to localise tumour etc in whole body
• 3D image or map of functional processes
• The system detects pairs of gamma-rays emitted indirectly by a positron (positively charged electron) emitting radioisotope (tracer) via annihilation events

Question 2

Detector in PET:

Answer 2

• Scanning device, where a burst of light created in scintillation crystal is detected by a photomultiplier tube or silicon avalanche photodiodes
• Ring of detectors around patient

Question 3

Localisation of the positron annihilation event:

Answer 3

• Results in two 511 keV gamma photons at almost 180 degrees -> localise source using ‘Line of Response’
• LOR has finite width
• Recovery time of detectors is in the picosecond range (TOF)

Question 4

Factors limiting resolution (x3):

Answer 4

• Distance of travel between radionuclide and annihilation event (‘error due to positron range’)
• Non-linearity of the two gamma-rays
• Sensitivity of detectors

Question 5

Active PET isotopes (4 organic and 4 metal):

Answer 5

• Organic (including O-15, N-13, C-11, F-18)
• Metal (including Ga-68, Cu-64, Y-86, Zr-89)

Question 6

Fluorine-18 based agents

Answer 6

• FDG
• Fluorine-18 half life of 109 mins
• Produced from H2(18)O + 1H+ -> 18F- + n
• Isolated in aqueous solution and extracted by ion exchange or in organic solvent
• Alternatively, can be produced from Neon

Question 7

Typical PET radionucleotides:

Answer 7

• Usually organic isotopes incorporated into either compounds normally used by the body or that bind to receptors/sites of drug action
• Some tracers distribute in tissues by partially following the metabolic pathways; others bind with specificity in the tissues containing the particular receptor proteins for which they have affinity

Question 8

PET radionuclide production:

Answer 8

• Typically a local cyclotron is used to produce
• Accelerating protons in electromagnetic field, collide with parent isotope -> alpha particle kicked out
• e.g. 14N2 + 1H+ -> 11C + alpha
• Requires fast chemistry

Question 9

FDG applications:

Answer 9

• Glucose analogue
• Widely used in clinical oncology
• Effectively non-toxic
• Taken up by glucose-using cells and phosphorylated by hexakinase (greatly elevated in rapidly-growing malignant tumours
• F-18 prevents this phosphorylation; doesn’t decompose and is stuck in cell
• Results in intense radiolabelling of tissues with high glucose uptake
• Used for diagnosis, staging and monitoring treatment of cancers, particularly Hodgkin’s disease, non Hodgkin’s lymphoma and lung cancer
• Often combined with CT and PET to give background image of body

Question 10

FDG synthesis:

Answer 10

• Mannose protected by acyl except one O which has Tf (good leaving group)
• Displaced by 18-F- in MeCN
• Deprotected by hydrolysis in HCl -> FDG
• Use automated synthesisers for reaction

Question 11

Advantages and disadvantages of FDG scans:

Answer 11

• Very low radiation dose, short-lived radionuclides
• Wide range of applications
• High cost of cyclotrons
• This restricts clinical PET based on very short half-lives
• Frequent recalibration required (remaining dose for day) and careful planning with respect to patient scheduling
• Not suitable for certain patients (e.g. diabetics)

Question 12

Neurology PET:

Answer 12

• Based on assumption that areas of high radioactivity associated with brain activity
• Measuring indirectly the flow of blood to different parts of the brain using 15-O piped directly from a medical cyclotron
• Certain pathologies (like AD) decrease brain metabolism
• Standard FDG-PET may be used to differentiate AD from other forms of dementia

Question 13

Specific radionuclides for neurology

Answer 13

• [11C] Raclopride studies function of dopaminergic synapses D2 receptors; selective and reversible
• Fluorodopa -> neurotransmission and cell processes; synaptic distribution of the store neurotransmitter - used clinically for the study of PD

Question 14

Copper-64 in PET

Answer 14

• 762 min half life
• Requires stable complexes
• Cu-ATSM has charge balanced, chelate, soft thiolates, conjugated system targeting tumour cells
• Reduced to Cu+ in hypoxic tumour cells -> cationic Cu+ retained
• Protonation may also be important (tumours acidic)

Question 15

89-Zr trastuzumab

Answer 15

• Antibody to HER-2 overexpressed in many tumours
• Immuno-PET; time for antibody to direct agent to tumour -> needs long half life

Question 16

Safety in PET

Answer 16

• Scanning is non-invasive; however, does involve exposure to ionizing radiation
• Total dose is small though