1: Bioorg Med Chem. 2009 Jan 1;17(1):49-56. Epub 2008 Nov 17. Radiosynthesis, in vitro and in vivo evaluation of 123I-labeled anandamide analogues for mapping brain FAAH. Wyffels L, De Bruyne S, Blanckaert P, Lambert DM, De Vos F. Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. leonie.wyffels@ugent.be 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. PMID: 19054678 [PubMed - indexed for MEDLINE] Related Links Inhibition of fatty acid amide hydrolase and monoacylglycerol lipase by the anandamide uptake inhibitor VDM11: evidence that VDM11 acts as an FAAH substrate. [Br J Pharmacol. 2005] PMID:15895107 Inhibition of fatty acid amide hydrolase, a key endocannabinoid metabolizing enzyme, by analogues of ibuprofen and indomethacin. [Eur J Pharmacol. 2007] PMID:17397826 FAAH and anandamide: is 2-AG really the odd one out? [Trends Pharmacol Sci. 2008] PMID:18394720 123I-MSP and F[11C]MSP: new selective 5-HT2A receptor radiopharmaceuticals for in vivo studies of neuronal 5-HT2 serotonin receptors. Synthesis, in vitro binding study with unlabelled analogues and preliminary in vivo evaluation in mice. [Life Sci. 1998] PMID:9839544 Pharmacological characterization of endocannabinoid transport and fatty acid amide hydrolase inhibitors. [Cell Mol Neurobiol. 2006] PMID:16736384