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.⁹⁰Y(iii), ¹⁷⁷Lu(iii) and ¹¹¹In(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 ¹¹¹In(iii) to obtain a new radiopharmaceutical product with potential applications in the diagnosis of tumors over-expressing oxytocin receptors.