Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT
| Autor: | Orhan K. Öz, Guiyang Hao, William Silvers, Tara Mastren, Gedaa Hassan, Xiankai Sun |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Immunoconjugates
medicine.drug_class Receptor ErbB-2 Science medicine.medical_treatment Mice SCID Monoclonal antibody Antibodies Monoclonal Humanized Article 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Trastuzumab Spect imaging Cell Line Tumor medicine Animals Humans Cancer Tomography Emission-Computed Single-Photon Multidisciplinary medicine.diagnostic_test business.industry Chemistry Immunotherapy Radioimmunotherapy medicine.disease Xenograft Model Antitumor Assays Copper Radioisotopes Oncology 030220 oncology & carcinogenesis Radionuclide therapy Medicine Female Pertuzumab Nuclear medicine business Tomography X-Ray Computed Emission computed tomography Biomarkers medicine.drug Biotechnology |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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