Development of Specific PET Tracers for Central Nervous System Drug Targets

Abstract

The development of biomarkers is key to the discovery of novel drugs. Positron emission tomography (PET) tracers are powerful noninvasive neuroimaging biomarkers which enable to monitor the target engagement of the central nervous system (CNS) drugs. This report describes the design, synthesis, and identification of specific PET tracers for CNS drug targets, namely, monoacylglycerol lipase ([¹⁸F]T-401), diacylglycerol kinase gamma ([¹¹C]T-278), lysine-specific demethylase 1 ([¹⁸F]T-914) and cholesterol 24-hydroxylase ([¹⁸F]T-008), based on screening flow customized for PET tracer discovery. Analyzing PET images of rodents and non-human primates confirmed that these tracers could serve as biomarkers to support the development of novel drugs.