PET is used in drug discovery:
- Drug PK through isotopic substitution can be easily done, microdosing studies, target engagement studies, drug drug interaction, drug delivery.
PET in patient selection
- Amyloid and Tau PET can help select patients
- Cancer staging and treatment allocation
- Targeted therapies
- Cardiac Evaluation
Process:
Cyclotron is used, chemistry and formulation and then imaging and analysis.
PET
Takes time to make the probe:
20 mins to make the probe
For brain usually short half life is used – Carbon 11 – 20 minutes, Fluorine 18 109 minutes, Nitrogen 13 10 minutes, Oxygen 15 (2 min)
60 minutes for chemistry
Chemistry for Carbon usually goes through 11CO2 – carbon dioxide.
Scan would take about 90 minutes.
2 Kinds of probe:
Receptor based – Raclopride – D2 receptors
FDG – Glucose metabolism
About 40 targets are available.
There is potential for ML/AI models for CNS – PET agent development
Most PET traces fail due to non-specific binding.
Monkey scans are usually used to see target engagement as well as drug treatment response.
Website : https://www.nimh.nih.gov/research/research-funded-by-nimh/therapeutics/cns-radiotracer-table