Synthesis of functionalised HP-DO3A chelating agents for conjugation to biomolecules

Two novel bifunctional chelating agents (BFCAs) based on the structure of 10-(2-hydroxypropyl)1,4,7-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) have been designed and synthesized. BFCAs are able to strongly coordinate metals (e. g. Gd(III)) and radiometals (e. g. Y-90(III), Lu-177(III) and In-111(III)), and find applications in the synthesis of products for the imaging and treatment of several cancer types. Indeed, these two BFCAs have been employed in solid-phase peptide synthesis (SPPS) and coupled to well-known peptides such as bombesin and RGD analogues in order to target tumor cells. We also report here the conjugation of one of them to Lys(8)-oxytocin and radiolabeling with In-111(III) to obtain a new radiopharmaceutical product with potential applications in the diagnosis of tumors over-expressing oxytocin receptors.