Radiolabeling Diaminosarcophagine with Cyclotron-Produced Cobalt-55 and [Co]Co-NT-Sarcage as a Proof of Concept in a Murine Xenograft Model.

Cobalt-sarcophagine complexes exhibit high kinetic inertness under various stringent conditions, but there is limited literature on radiolabeling and in vivo positron emission tomography (PET) imaging using no carrier added Co. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with Co, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [Co]CoCl to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [Co]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice. The [Co]Co-DSar complex can be formed at 37 °C with purity and stability suitable for preclinical in vivo radiopharmaceutical applications, and [Co]Co-NT-Sarcage demonstrated prominent tumor uptake with a low background signal. In a direct comparison with [Cu]Cu-NT-Sarcage, [Co]Co-NT-Sarcage achieved a higher tumor-to-liver ratio but with overall similar biodistribution profile. These results demonstrate that Sar would be a promising chelator for constructing Co-based radiopharmaceuticals including Co for PET and Co for therapeutic applications.