Copper-67 Radioimmunotheranostics for Simultaneous Immunotherapy and Immuno-SPECT

Copper-67 (t = 2.58 days) decays by β ([Formula: see text]: 562 keV) and γ-rays (93 keV and 185 keV) rendering it with potential for both radionuclide therapy and single-photon emission computed tomography (SPECT) imaging. Prompted by the recent breakthrough of Cu production with high specific activity, high radionuclidic purity, and sufficient quantities, the interest in the theranostic potential of Cu has been rekindled. This work addresses the practicability of developing Cu-labeled antibodies with substantially improved quality for cancer radioimmunotheranostics. Proof of concept is demonstrated with pertuzumab, a US-FDA-approved monoclonal antibody for combination therapies of HER2-positive breast cancer. With an average number of 1.9 chelators coupled to each antibody, we achieved a two-order of magnitude increase in radiolabeling efficiency compared to literature reports. In a preclinical therapeutic study, mice (n = 4-7/group) bearing HER2 xenografts exhibited a Cu-dose dependent tumor-growth inhibition from Cu-labeled-Pertuzumab co-administered with trastuzumab. Furthermore, greater tumor size reduction was observed with Cu-labeled-pertuzumab formulations of higher specific activity. The potential of SPECT imaging with Cu radiopharmaceuticals was tested after Cu-labeled-Pertuzumab administration. Impressively, all tumors were clearly visualized by SPECT imaging with Cu-labeled-Pertuzumab even at day 5 post injection. This work demonstrates it is practical to use Cu radioimmunoconjugates for cancer radioimmunotheranostics.