摘要：Abstract Copper-67 (t 1/2 = 2.58 days) decays by β − ( $$\text{E}_{{\upbeta^{-}\text{max}}}$$ E β - 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 67 Cu production with high specific activity, high radionuclidic purity, and sufficient quantities, the interest in the theranostic potential of 67 Cu has been rekindled. This work addresses the practicability of developing 67 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 67 Cu-dose dependent tumor-growth inhibition from 67 Cu-labeled-Pertuzumab co-administered with trastuzumab. Furthermore, greater tumor size reduction was observed with 67 Cu-labeled-pertuzumab formulations of higher specific activity. The potential of SPECT imaging with 67 Cu radiopharmaceuticals was tested after 67 Cu-labeled-Pertuzumab administration. Impressively, all tumors were clearly visualized by SPECT imaging with 67 Cu-labeled-Pertuzumab even at day 5 post injection. This work demonstrates it is practical to use 67 Cu radioimmunoconjugates for cancer radioimmunotheranostics.
其他摘要：Abstract Copper-67 (t 1/2 = 2.58 days) decays by β − ( $$\text{E}_{{\upbeta^{-}\text{max}}}$$ E β - 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 67 Cu production with high specific activity, high radionuclidic purity, and sufficient quantities, the interest in the theranostic potential of 67 Cu has been rekindled. This work addresses the practicability of developing 67 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 67 Cu-dose dependent tumor-growth inhibition from 67 Cu-labeled-Pertuzumab co-administered with trastuzumab. Furthermore, greater tumor size reduction was observed with 67 Cu-labeled-pertuzumab formulations of higher specific activity. The potential of SPECT imaging with 67 Cu radiopharmaceuticals was tested after 67 Cu-labeled-Pertuzumab administration. Impressively, all tumors were clearly visualized by SPECT imaging with 67 Cu-labeled-Pertuzumab even at day 5 post injection. This work demonstrates it is practical to use 67 Cu radioimmunoconjugates for cancer radioimmunotheranostics.
