Imaging Autotaxin In Vivo with 18F-Labeled Positron Emission Tomography Ligands

Le résumé fourni par la source

Autotaxin (ATX) is a secreted phosphodiesterase that has been implicated in a remarkably wide array of pathologies, especially in fibrosis and cancer. While ATX inhibitors have entered the clinical arena, a validated probe for positron emission tomography (PET) is currently lacking. With the aim to develop a suitable ATX-targeted PET radioligand, we have synthesized a focused library of fluorinated imidazo[1,2- a ]pyridine derivatives, determined their inhibition constants, and confirmed their binding mode by crystallographic analysis. Based on their promising in vitro properties, compounds 9c, 9f, 9h, and 9j were radiofluorinated. Also, a deuterated analog of [ 18 F] 9j, designated as [ 18 F]ATX-1905 ([ 18 F] 20 ), was designed and proved to be highly stable against in vivo radiodefluorination compared with [ 18 F] 9c, [ 18 F] 9f, [ 18 F] 9h, and [ 18 F] 9j . These results along with in vitro and in vivo studies toward ATX in a mouse model of LPS-induced liver injury suggest that [ 18 F]ATX-1905 is a suitable PET probe for the non-invasive quantification of ATX.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.