Radiolabeling Diaminosarcophagine with Cyclotron-Produced Cobalt-55 and [⁵⁵Co]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-55. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with Co-55, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [Co-55]CoCl2 to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [Co-55]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice. The [Co-55]Co-DSar complex can be formed at 37 degrees C with purity and stability suitable for preclinical in vivo radiopharmaceutical applications, and [Co-55]Co-NT-Sarcage demonstrated prominent tumor uptake with a low background signal. In a direct comparison with [Cu-64]Cu-NT-Sarcage, [Co-55]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-55 for PET and Co-58m for therapeutic applications.