Development of the High-Affinity Carborane-Based Cannabinoid Receptor Type 2 PET Ligand [F]LUZ5-.

The development of cannabinoid receptor type 2 (CBR) radioligands for positron emission tomography (PET) imaging was intensively explored. To overcome the low metabolic stability and simultaneously increase the binding affinity of known CBR radioligands, a carborane moiety was used as a bioisostere. Here we report the synthesis and characterization of carborane-based 1,8-naphthyridinones and thiazoles as novel CBR ligands. All tested compounds showed low nanomolar CBR affinity, with ()--[3-(4-fluorobutyl)-4,5-dimethylthiazole-2(3)-ylidene]-(1,7-dicarba--dodecaboranyl)-carboxamide () exhibiting the highest affinity (0.8 nM). Compound was obtained with an automated radiosynthesizer in high radiochemical yield and purity. evaluation revealed the improved metabolic stability of compared to that of . PET experiments in rats revealed high uptake in spleen and low uptake in brain. Thus, the introduction of a carborane moiety is an appropriate tool for modifying literature-known CBR ligands and gaining access to a new class of high-affinity CBR ligands, while the pharmacology still needs to be addressed.