PET – positron emission tomography
PET is a 3-D imaging technique that can assess distribution, receptor occupancy, and pharmacodynamic effects of a radiolabelled ligand (agonist or antagonist) in man. In drug development, PET can
- help choose a lead candidate
- predict the dose
- predict the dosing interval
- show proof-of-principle
- predict disease
PET trials are demanding, require specialist techniques, and are more resource‑intensive than typical Phase 1 trials. We collaborate with Invicro at Hammersmith Hospital, London, and together we’re leading providers of PET and MRI in drug development.
PET uses a radionuclide – usually 11C, in trials of IMPs. The 11C emits positrons, which travel less than 1 mm before colliding with electrons in atoms in the surrounding tissues. The positron and electron destroy each other, and emit 2 photons at 180° to each other.
Invicro uses a cyclotron to radiolabel the ligand, which is then given to a subject lying in a PET scanner. Photons escaping from the body are detected by the scanner, yielding a dynamic, 3-D image that reflects quantitatively the distribution of the radionuclide in the body over time.
Because the 11C radionuclide has such a short half-life, the cyclotron and PET scanner must be close to each other, and the subject must receive the radioligand soon after it has been made.
Only specialised centres can do PET trials. HMR recruits the subjects, does the clinical work, and runs the trial. Invicro prepares the radioligand, does the PET scans, and analyses and interprets the results. Since 1993 we’ve done about 60 trials in healthy subjects or patients, to assess new drugs acting at targets such as dopamine D2, adenosineA2A, benzodiazepine, MAO, neurotropin, NK1, and GABA receptors. We’ve studied medicines to treat conditions including schizophrenia, Parkinson’s, Alzheimer’s and depression.
HMR resources and trial set-up
- We’ve a large recruitment and screening team, experienced in PET trials
- HMR is just a 10–20 min drive from Invicro
- an HMR physician and nurse are at Invicro throughout the entire procedure
- HMR staff do all the usual trial procedures (blood sampling, ECG, etc) when subjects aren’t in the PET scanner. We process blood samples at Invicro, and organise storage, shipment & analysis
- We’ve never failed to complete a PET trial in a timely manner
Some of our publications
- Bench C, Lammertsma A, Dolan R, Grasby P, Warrington S, Gunn K, Cuddigan M, Turton D, Osman S, Frackowiak R. Dose-dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: study using PET and 11C-raclopride. Psychopharmacology 1993; 112: 308–314
- Bench C, Lammertsma A, Grasby P, Dolan R, Warrington S, Boyce M, Gunn K, Brannick L, Frackowiak R. The time course of occupancy of striatal dopamine D2 receptors by the neuroleptic ziprasidone (CP-88,059-01) determined by PET. Psychopharmacology 1996; 124: 141–147
- Brooks D et al. An open-label, positron emission tomography study to assess adenosine A2A brain receptor occupancy of vipadenant (BIIB014) at steady-state levels in healthy male volunteers. Clinical Neuropharmacology 2010; 33: 55–60