A Multifunctional HBED-Type Chelator with Dual Conjugation Capabilities for Radiopharmaceutical Development

Abstract

Bifunctional HBED chelators are hexadentate complexing ligands (chelators) that tightly coordinate to trivalent gallium and, additionally, are able to bind to bioactive molecules. In nuclear medicine, HBED-based radiopharmaceuticals are used as powerful radiotracers for tumor imaging. Among variants of bifunctional HBED chelators, HBED-CC is the most well-known; it possesses two terminal carboxylic acid groups that are able to undergo bioconjugation by amide-bond formation. However, to permit bioconjugation through click coupling, we previously modified the structure of HBED-CC and introduced HBED-NN chelator bearing two azide functions. We have now combined the conjugation capabilities of HBED-CC and HBED-NN chelators in one molecule and have created HBED-NC, which possesses both azide and carboxylic acid groups. The advantage of HBED-NC is that it provides options for constructing either monomeric or heterodimeric radiolabeling precursors. This work describes the synthesis of HBED-NC by either of two pathways.