Title
Radiosynthesis, in vitro and in vivo evaluation of <tex>$^{123}I$</tex>-labeled anandamide analogues for mapping brain FAAH Radiosynthesis, in vitro and in vivo evaluation of <tex>$^{123}I$</tex>-labeled anandamide analogues for mapping brain FAAH
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Oxford ,
Subject
Pharmacology. Therapy
Source (journal)
Bioorganic and medicinal chemistry. - Oxford
Volume/pages
17(2009) :1 , p. 49-56
ISSN
0968-0896
ISI
000261909800006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
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 μM and 3.14 μM, 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.
E-info
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