Radiosynthesis, in vitro and in vivo evaluation of <script type="math/tex">^{123}I</script>-labeled anandamide analogues for mapping brain FAAH

Wyffels, Leonie; De Bruyne, Sylvie; Blanckaert, Peter; Lambert, Didier M.; De Vos, Filip

doi:10.1016/J.BMC.2008.11.019

Title

Radiosynthesis, in vitro and in vivo evaluation of $^{123}I$ -labeled anandamide analogues for mapping brain FAAH

Author

Wyffels, Leonie

De Bruyne, Sylvie

Blanckaert, Peter

Lambert, Didier M.

De Vos, Filip

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.

Language

English

Source (journal)

Bioorganic and medicinal chemistry. - Oxford

Publication

Oxford : 2009

ISSN

0968-0896

DOI

10.1016/J.BMC.2008.11.019

Volume/pages

17 :1 (2009) , p. 49-56