Principles of PET and its role in understanding drug delivery to the brain

Abstract

Positron emission tomography (PET) is a non-invasive medical imaging technique that enables the investigation of drug pharmacokinetics in vivo. The technique is especially powerful for pharmacokinetic studies of new CNS drug candidates as tissue samples from the brain are understandably difficult to obtain. The PET technique involves the administration of a radiolabelled molecule whose spatio-temporal distribution can be measured using tomography. The radiolabelled molecule can be the drug under investigation, a structurally different molecule that binds to the same target as the drug candidate or a molecule that interacts with a downstream target that is believed to be affected by the action of the drug candidate. Such radiolabelled probes allow PET to address several questions central for CNS drug development: Does the drug candidate reach the target site? Does the drug candidate interact with the desired target? Is the concentration of the drug at the target site sufficient to illicit an effect? What is the temporal nature of such an interaction? What is the relationship between the target site concentration and the administered dose and/or plasma concentrations?