Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT

Copper-67 (t_1/2 = 2.58 days) decays by β⁻ (Eβ-max: 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 ⁶⁷Cu production with high specific activity, high radionuclidic purity, and sufficient quantities, the interest in the theranostic potential of ⁶⁷Cu has been rekindled. This work addresses the practicability of developing ⁶⁷Cu-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 ⁶⁷Cu-dose dependent tumor-growth inhibition from ⁶⁷Cu-labeled-Pertuzumab co-administered with trastuzumab. Furthermore, greater tumor size reduction was observed with ⁶⁷Cu-labeled-pertuzumab formulations of higher specific activity. The potential of SPECT imaging with ⁶⁷Cu radiopharmaceuticals was tested after ⁶⁷Cu-labeled-Pertuzumab administration. Impressively, all tumors were clearly visualized by SPECT imaging with ⁶⁷Cu-labeled-Pertuzumab even at day 5 post injection. This work demonstrates it is practical to use ⁶⁷Cu radioimmunoconjugates for cancer radioimmunotheranostics.