Controlling the Redox Chemistry of Cobalt Radiopharmaceuticals

Abstract The elementally matched 55 Co 2+/3+ (t 1/2 =17.53 h, I β+ =77 %)/ 58m Co 2+/3+ (t 1/2 =9.10 h, internal conversion=100 %) radioisotope pair is of interest for development of paired diagnostic/therapeutic radiopharmaceuticals. Due to the accessibility of the nat/55 Co 2+/3+ redox couple, the redox state can be readily modulated. Here, we show that macroscopic and radiochemical redox reactions can be closely monitored and controlled using spectroscopic and radiochemical methods. We employ model systems to inform how to selectively synthesize thermodynamically favored oxidation state coordination complexes. In addition to exogenous oxidants, our data indicates that 55 Co‐induced radiolysis of water efficiently and directly drives selective oxidation to the 55 Co 3+ species under no‐carrier added (n.c.a.) conditions. Our synthetic strategies subsequently stabilize the respective 55 Co 2+ or 55 Co 3+ species for targeted positron emission tomography imaging in a mouse tumor model.