Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

Abstract In this work, we report on a synthetic strategy using amphiphilic DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelators bearing a variable-sized α-alkyl chain at one of the pendant acetate arms (from 6 to 14 carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micellar concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the67 Ga-labeled chelates were performed in Wistar rats, which showed a predominant liver uptake with almost no traces of the radiochelates in the body after 24 h.