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]

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