Design, Synthesis, and Evaluation of 18 F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes.

Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound 6 (identified from a therapeutic agent) was advanced for ¹⁸ F-labeling via a novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability and excellent specific binding. This work supports further development of novel ¹⁸ F-labeled MAGL PET probes.