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

Abstract

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