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.
Charalambous
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Department of Medicinal Chemistry, School of Pharmacy, University of Connecticut, Storrs 06269-2092.
Marciniak
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G
Shiue
C Y
CY
Dewey
S L
SL
Schlyer
D J
DJ
Wolf
A P
AP
Makriyannis
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A
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010215:Papio; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; C035731:delta-8-tetrahydrocannabinol; D013759:Dronabinol