Synthesis of 18F-labeled nitrogen heterocyclic derivatives as new candidate for cannabinoid CB2 receptor PET imaging

The endocannabinoid system is involved in a growing number of physiological functions, both in central and peripheral nervous system and in peripheral organs. This system includes two G-protein-coupled transmembrane receptors named CB1 and CB2. In normal brain, it's mainly present CB1R whereas CB2R has a low expression. However, only recently CB2R has been suggested as a mediator of several central and peripheral inflammatory diseases. This receptor population is indeed up-regulated in some pathological conditions such as amyotrophic lateral sclerosis, multiple sclerosis, stroke and Alzheimer. Peripheral CB2R up-regulation has been also demonstrated in several cancer, endometrial inflammation and human and murine atherosclerotic plaques. In this work, we report the design and synthesis of [18F]-labeled naphthyridine, quinoline, and pyridine derivatives as PET tracers for in vivo visualization of the CB2R. This operation will provide a diagnostic tool for noninvasive imaging of cancer and/or neuroinflammation pathologies and monitoring of therapeutic efficacy. The corresponding unlabeled molecules have been previously synthesized by our group and showed remarkable affinity on CB2R (Ki < 10 nM).