1. J Med Chem. 2009 Aug 13;52(15):4613-22.

Synthesis, in vitro and in vivo evaluation, and radiolabeling of aryl anandamide 
analogues as candidate radioligands for in vivo imaging of fatty acid amide
hydrolase in the brain.

Wyffels L, Muccioli GG, De Bruyne S, Moerman L, Sambre J, Lambert DM, De Vos F.

Department of Radiopharmacy, Ghent University, Harelbekestraat 72, B-9000 Ghent, 
Belgium.

Fatty acid amide hydrolyase (FAAH) is one of the main enzymes responsible for
terminating the signaling of endocannabinoids in the brain. Imaging FAAH in vivo 
using PET or SPECT is important to deeper understanding of its role in
neuropsychiatric disorders. However, at present, no radioligand is available for 
mapping the enzyme in vivo. Here, we synthesized 18 aryl analogues of anandamide,
FAAH's endogenous substrate, and in vitro evaluated their potential as metabolic 
trapping tracers. Interaction studies with recombinant FAAH revealed good to very
good interaction of the methoxy substituted aryl anandamide analogues 17, 18, 19,
and 20 with FAAH and they were identified as competing substrates. Compounds 17
and 18 did not display significant binding to CB1 and CB2 cannabinoid receptors
and stand out as potential candidate metabolic trapping tracers. They were
successfully labeled with 11C in good yields and high radiochemical purity and
displayed brain uptake in C57BL/6J mice. Radioligands [11C]-17 and [11C]-18 merit
further investigation in vivo.

PMID: 19719235 [PubMed - indexed for MEDLINE]