title: Radiosynthesis, in vitro and in vivo evaluation of 123I-labeled anandamide analogues for mapping brain FAAH.
abstract: 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.
authors.affiliation: Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. leonie.wyffels@ugent.be
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
authors.forename: Sylvie
authors.initials: S
authors.lastname: De Bruyne
authors.forename: Peter
authors.initials: P
authors.lastname: Blanckaert
authors.forename: Didier M
authors.initials: DM
authors.lastname: Lambert
authors.forename: Filip
authors.initials: F
authors.lastname: De Vos
mesh_terms: 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
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D007457:Iodine Radioisotopes; D053284:Polyunsaturated Alkamides; D019275:Radiopharmaceuticals; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide