Controlling the Redox Chemistry of Cobalt Radiopharmaceuticals

The elementally matched ⁵⁵Co^2+/3+ (t_1/2=17.53 h, I_β+=77 %)/^58mCo^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/55Co^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 ⁵⁵Co-induced radiolysis of water efficiently and directly drives selective oxidation to the ⁵⁵Co³⁺ species under no-carrier added (n.c.a.) conditions. Our synthetic strategies subsequently stabilize the respective ⁵⁵Co²⁺ or ⁵⁵Co³⁺ species for targeted positron emission tomography imaging in a mouse tumor model.