PET studies in the primate brain and biodistribution in mice using (-)-5'-18F-delta 8-THC

Cannabinoids, the active constituents of marijuana, are known to have many therapeutic properties; however, their exact mechanism of action is not well understood. In an effort to obtain more information concerning the pharmacokinetics and biodistribution of psychoactive THC analogs we synthesized (-)-18F-delta 8-THC and studied its biodistribution in mice and baboon brains. The analog was obtained by nucleophilic fluorination of the ditriflate ester of (-)-5'-OH-delta 8-THC with K18F/Kryptofix followed by deprotection with LiAIH4 and purification with HPLC in 8% yield in a 90-min synthesis from EOB. The uptake of (-)-5'-18F-delta 8-THC in mouse tissue was high at 5 min, but radioactivity declined rapidly in almost all the tissues studied. Following IV administration, (-)-5'-18F-delta 8-THC uptake in baboon brain was similar in the basal ganglia, thalamus and cerebellum, and the clearance from these regions was relatively rapid. Also, a study from baboon plasma clearance of (-)-5'-18F-delta 8-THC showed rapid metabolism of the analog.