Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT.
Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT.
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DOI：
10.1038/s41598-021-82812-1
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发表时间：
2021-02-11
影响因子：
4.6
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Hao G;Mastren T;Silvers W;Hassan G;Öz OK;Sun X
铜-67(T1/2 = 2.58天)被β−(：562 keV)和γ射线(93 keV和185 keV)衰减，使其具有放射性核素治疗和单光子发射计算机断层成像的潜力。由于最近取得的高比活度、高放射性核素纯度和足够数量的67Cu生产的突破，人们对67Cu的热释光潜力重新燃起了兴趣。这项工作解决了开发67Cu标记抗体的可行性，大大提高了癌症放射免疫分析的质量。概念验证是用pertuzumab，一种美国FDA批准的用于联合治疗HER2阳性乳腺癌的单抗。平均每个抗体上有1.9个螯合剂，与文献报道相比，我们实现了放射性标记效率的两个数量级的提高。在一项临床前治疗研究中，携带HER2+的小鼠(n = 4-7/组)与曲妥珠单抗联合应用，显示出67Cu剂量依赖性的肿瘤生长抑制作用。此外，比活性更高的67Cu标记的pertuzumab制剂观察到更大的肿瘤体积缩小。用~(67)Cu标记的Pertuzumab对~(67)Cu放射性药物进行SPECT显像。令人印象深刻的是，即使在注射后第5天，67Cu标记的Pertuzumab SPECT成像也能清楚地显示所有肿瘤。这项工作证明了将67Cu放射免疫结合物用于癌症放射免疫治疗是可行的。
Copper-67 (t1/2 = 2.58 days) decays by β− (: 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.
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影响因子：
9.3
作者：
Cullinane, Carleen;Jeffery, Charmaine M.;Donnelly, Paul S.
通讯作者：
Donnelly, Paul S.
DOI：
10.1007/bf00881818
发表时间：
1997-04-01
期刊：
EUROPEAN JOURNAL OF NUCLEAR MEDICINE
影响因子：
--
作者：
Hughes, ODM;Bishop, MC;Schubiger, PA
通讯作者：
Schubiger, PA
DOI：
10.1007/s10967-007-7144-9
发表时间：
2008-08-01
影响因子：
1.6
作者：
Katabuchi, T.;Watanabe, S.;Matsuhashi, S.
通讯作者：
Matsuhashi, S.
影响因子：
1.6
作者：
Mausner, LF;Kolsky, KL;Srivastava, SC
通讯作者：
Srivastava, SC
影响因子：
1.6
作者：
Al-Abyad, M;Spahn, I;Coenen, HH
通讯作者：
Coenen, HH