Coordination-Mediated Synthesis of 67 Ga-Labeled Purification-Free Trivalent Probes for in Vivo Imaging of Saturable Systems

A large excess of unlabeled ligands over gallium-67 ( Ga) provides Ga-labeled probes with high radiochemical yields in a short reaction time. However, the unlabeled ligands hinder target accumulation of radiolabeled probes by competing for target molecules. To circumvent the problem, we investigated the way to prepare Ga-labeled multivalent probes from monovalent ligands. The reaction of a bi- or tridentate ligand with [ Ga]Ga-citrate resulted in Ga-labeled probes of insufficient stability. However, the reaction of [ Ga]Ga-citrate with a mixture of RGD-conjugated salicylaldehyde and triamine provided a Ga-labeled trivalent probe with stability sufficient for in vivo applications. Since the free Schiff base ligand decomposed rapidly upon injection, the Ga-labeled trivalent probe visualized the murine tumor without postlabeling purification, which was not achieved with a Ga-labeled trivalent probe from a trivalent ligand. These findings indicate the availability of Schiff base ligands to prepare Ga-labeled trivalent probes by a simple radiolabeling procedure.