Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Sci Rep. 2021 Feb 11;11(1):3622. doi: 10.1038/s41598-021-82812-1.
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.
铜-67（t=2.58 天）通过 β 衰变（[公式：见正文]：562keV）和γ射线（93keV 和 185keV）衰变，具有放射性核素治疗和单光子发射计算机断层扫描（SPECT）成像的潜力。由于最近在高比活度、高放射性核纯度和足够数量的铜生产方面取得了突破，铜的治疗潜力重新引起了人们的兴趣。这项工作探讨了开发具有显著提高质量的放射性核素标记抗体用于癌症放射免疫治疗的可行性。使用曲妥珠单抗（一种美国食品和药物管理局批准的用于治疗 HER2 阳性乳腺癌的单克隆抗体）证明了这一概念。通过每个抗体偶联 1.9 个螯合剂，与文献报道相比，放射性标记效率提高了两个数量级。在临床前治疗研究中，荷 HER2 异种移植瘤的小鼠（n=4-7/组）在接受曲妥珠单抗联合 Cu 标记-Pertuzumab 治疗后表现出 Cu 剂量依赖性的肿瘤生长抑制。此外，观察到具有更高比活度的 Cu 标记-pertuzumab 制剂的肿瘤体积缩小更大。在给予 Cu 标记-Pertuzumab 后，测试了 Cu 放射性药物的 SPECT 成像的潜力。令人印象深刻的是，即使在注射后第 5 天，所有肿瘤都可以通过 SPECT 成像清晰地显示出 Cu 标记-Pertuzumab。这项工作表明，使用 Cu 放射性免疫偶联物进行癌症放射免疫治疗是可行的。
