Radiosynthesis, in vitro and in vivo evaluation of 123I-labeled anandamide analogues for mapping brain FAAH.
Fatty acid amide hydrolase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids, including anandamide. This paper is the first report of the synthesis, [123I]-labeling and in vitro and in vivo evaluation of anandamide analogues as potential metabolic trapping radioligands for in vivo evaluation of brain FAAH. N-(2-iodoethyl)linoleoylamide (2) and N-(2-iodoethyl)arachidonylamide (4) were synthesized with good yields (75% and 86%, respectively) in a two steps procedure starting from their respective acids. In vitro analyses, performed using recombinant rat FAAH and [3H]-anandamide, demonstrated interaction of 2 and 4 with FAAH (IC50 values of 5.78 microM and 3.14 microM, respectively). [123I]-2 and [123I]-4 were synthesized with radiochemical yields of 21% and 12%, respectively, and radiochemical purities were > 90%. Biodistribution studies in mice demonstrated brain uptake for both tracers (maximum values of 1.23%ID/g at 3 min pi for [123I]-2 and 0.58%ID/g at 10 min pi for [123I]-4). However, stability studies demonstrated the sensitivity of both tracers to dehalogenation.
Wyffels
Leonie
L
Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. leonie.wyffels@ugent.be
De Bruyne
Sylvie
S
Blanckaert
Peter
P
Lambert
Didier M
DM
De Vos
Filip
F
D000581:Amidohydrolases / Q000032:analysis*; D000818:Animals; D001095:Arachidonic Acids / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D001931:Brain Mapping; D063388:Endocannabinoids; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D053284:Polyunsaturated Alkamides / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D007457:Iodine Radioisotopes; D053284:Polyunsaturated Alkamides; D019275:Radiopharmaceuticals; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide