Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT
Abstract Copper-67 (t1/2 = 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 breakthrou...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-82812-1 |
| _version_ | 1818841798980665344 |
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| author | Guiyang Hao Tara Mastren William Silvers Gedaa Hassan Orhan K. Öz Xiankai Sun |
| author_facet | Guiyang Hao Tara Mastren William Silvers Gedaa Hassan Orhan K. Öz Xiankai Sun |
| author_sort | Guiyang Hao |
| collection | DOAJ |
| description | Abstract Copper-67 (t1/2 = 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 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. |
| first_indexed | 2024-12-19T04:31:49Z |
| format | Article |
| id | doaj.art-bd8333e81bf24b33981c236b7c5fe9b7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:31:49Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-bd8333e81bf24b33981c236b7c5fe9b72022-12-21T20:35:52ZengNature PortfolioScientific Reports2045-23222021-02-0111111110.1038/s41598-021-82812-1Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECTGuiyang Hao0Tara Mastren1William Silvers2Gedaa Hassan3Orhan K. Öz4Xiankai Sun5Department of Radiology, University of Texas Southwestern Medical CenterDepartment of Radiology, University of Texas Southwestern Medical CenterDepartment of Radiology, University of Texas Southwestern Medical CenterDepartment of Radiology, University of Texas Southwestern Medical CenterDepartment of Radiology, University of Texas Southwestern Medical CenterDepartment of Radiology, University of Texas Southwestern Medical CenterAbstract Copper-67 (t1/2 = 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 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.https://doi.org/10.1038/s41598-021-82812-1 |
| spellingShingle | Guiyang Hao Tara Mastren William Silvers Gedaa Hassan Orhan K. Öz Xiankai Sun Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT Scientific Reports |
| title | Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT |
| title_full | Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT |
| title_fullStr | Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT |
| title_full_unstemmed | Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT |
| title_short | Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT |
| title_sort | copper 67 radioimmunotheranostics for simultaneous immunotherapy and immuno spect |
| url | https://doi.org/10.1038/s41598-021-82812-1 |
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