Abstract

A novel RuII(arene) theranostic complex is presented. It is based on a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocycle bearing a triarylphosphine and can be tracked in vivo by using the γ emission of 153Sm atoms. Notably, the heteroditopic ligand can be selectively metalated with ruthenium at the phosphorus atom despite the presence of other functionalities that are prone to metal coordination. Subsequent labeling with radionuclides such as 153Sm can then be performed easily. The resulting heterobimetallic complex exhibits favorable solubility and stability properties in biologically relevant media. It also shows in vitro cytotoxicity in line with that expected for this type of metallodrug, and is nontoxic to the organism as a whole. As a proof of concept, initial studies in healthy mice were performed to obtain information about the uptake, biodistribution, and excretion of the radiolabeled complex. Two metals better than one: A novel RuII(arene) theranostic complex is based on a new 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocycle bearing a triarylphosphine and can be tracked in vivo. The heteroditopic ligand can be sequentially and selectively metalated (first with Ru, then with 153Sm). The resulting heterobimetallic complex exhibits interesting cytotoxicity, water solubility, and stability. Initial biodistribution studies in healthy mice were performed as a proof of concept. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.