Strategies for designing novel PET radiotracers to cross the blood brain barrier

Positron emission tomography (PET) is a powerful tool for imaging biological processes in the central nervous system (CNS). Designing PET radiotracers capable of crossing the blood-brain barrier (BBB) remains a major challenge. In addition to being brain-penetrant, a quantifiable CNS PET radiotracer must have high target affinity and selectivity, appropriate pharmacokinetics, minimal non-specific binding, negligible radiometabolites in the brain, and must be amenable to labelling with11C or18F. This review aims to give an overview of some of the critical physicochemical and biochemical contributors specific for CNS PET radiotracer design and how they can differ from pharmaceutical drug development, including invitro assays,in silico predictions andin vivo studies, with examples for how such methods can be implemented to optimize brain uptake of radiotracers based on experiences from our neuroimaging program.
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: REVIEW Source Type: research