Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64
Understanding the physicochemical properties of antibody–drug conjugates is critical to assess their quality at manufacturing and monitor them during subsequent storage. For radiometal–antibody complexes, it is important to control the properties of the antibody–chelator conjugate to maintain the qu...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1341 |
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| author | Yukie Yoshii Hiroki Matsumoto Chika Igarashi Tomoko Tachibana Fukiko Hihara Mitsuhiro Shinada Atsuo Waki Sei Yoshida Kenichiro Naito Kimiteru Ito Tatsuya Higashi Hiroaki Kurihara Makoto Ueno |
| author_facet | Yukie Yoshii Hiroki Matsumoto Chika Igarashi Tomoko Tachibana Fukiko Hihara Mitsuhiro Shinada Atsuo Waki Sei Yoshida Kenichiro Naito Kimiteru Ito Tatsuya Higashi Hiroaki Kurihara Makoto Ueno |
| author_sort | Yukie Yoshii |
| collection | DOAJ |
| description | Understanding the physicochemical properties of antibody–drug conjugates is critical to assess their quality at manufacturing and monitor them during subsequent storage. For radiometal–antibody complexes, it is important to control the properties of the antibody–chelator conjugate to maintain the quality of the final product. We have been developing <sup>64</sup>Cu-labeled anti-epidermal growth factor receptor antibody NCAB001 (<sup>64</sup>Cu-NCAB001) for the early diagnosis and therapy of pancreatic cancer with positron-emission tomography. Here, we characterized the larger size variants contained in the antibody–chelator conjugate PCTA-NCAB001 by multi-angle light scattering coupled with size-exclusion chromatography. Secondly, we developed a chromatographic method to remove these size variants. Lastly, we demonstrated the stability of PCTA-NCAB001 after the removal of size variants. Dimer and oligomers were identified in PCTA-NCAB001. These larger size variants, together with some smaller size variants, could be removed by hydrophobic interaction chromatography. The PCTA-NCAB001 product, after the removal of these size variants, could be stored at 4 °C for six months. The methods developed here can be applied to assure the quality of PCTA-NCAB001 and other antibody–drug conjugates to facilitate the development of antibody–radiometal conjugates for positron-emission tomography and radioimmunotherapy of malignant cancers. |
| first_indexed | 2024-03-10T20:58:46Z |
| format | Article |
| id | doaj.art-7b2fb5433caf4e8faa8f63f71d8cb5a2 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:58:46Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-7b2fb5433caf4e8faa8f63f71d8cb5a22023-11-19T17:41:05ZengMDPI AGPharmaceuticals1424-82472023-09-011610134110.3390/ph16101341Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64Yukie Yoshii0Hiroki Matsumoto1Chika Igarashi2Tomoko Tachibana3Fukiko Hihara4Mitsuhiro Shinada5Atsuo Waki6Sei Yoshida7Kenichiro Naito8Kimiteru Ito9Tatsuya Higashi10Hiroaki Kurihara11Makoto Ueno12Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanInstitute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanInstitute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanInstitute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanInstitute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanInstitute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanInstitute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanDepartment of Research, NanoCarrier Co., Ltd., Tokyo 104-0031, JapanDepartment of Research, NanoCarrier Co., Ltd., Tokyo 104-0031, JapanDepartment of Diagnostic Radiology, National Cancer Center Hospital, Tokyo 104-0045, JapanInstitute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanDepartment of Diagnostic Radiology, Kanagawa Cancer Center, Yokohama 241-8515, JapanDepartment of Gastroenterology, Kanagawa Cancer Center, Yokohama 241-8515, JapanUnderstanding the physicochemical properties of antibody–drug conjugates is critical to assess their quality at manufacturing and monitor them during subsequent storage. For radiometal–antibody complexes, it is important to control the properties of the antibody–chelator conjugate to maintain the quality of the final product. We have been developing <sup>64</sup>Cu-labeled anti-epidermal growth factor receptor antibody NCAB001 (<sup>64</sup>Cu-NCAB001) for the early diagnosis and therapy of pancreatic cancer with positron-emission tomography. Here, we characterized the larger size variants contained in the antibody–chelator conjugate PCTA-NCAB001 by multi-angle light scattering coupled with size-exclusion chromatography. Secondly, we developed a chromatographic method to remove these size variants. Lastly, we demonstrated the stability of PCTA-NCAB001 after the removal of size variants. Dimer and oligomers were identified in PCTA-NCAB001. These larger size variants, together with some smaller size variants, could be removed by hydrophobic interaction chromatography. The PCTA-NCAB001 product, after the removal of these size variants, could be stored at 4 °C for six months. The methods developed here can be applied to assure the quality of PCTA-NCAB001 and other antibody–drug conjugates to facilitate the development of antibody–radiometal conjugates for positron-emission tomography and radioimmunotherapy of malignant cancers.https://www.mdpi.com/1424-8247/16/10/1341antibody–drug conjugatesantibody–chelator conjugateschromatographysize exclusionmulti-angle light scatteringhydrophobic interaction chromatography |
| spellingShingle | Yukie Yoshii Hiroki Matsumoto Chika Igarashi Tomoko Tachibana Fukiko Hihara Mitsuhiro Shinada Atsuo Waki Sei Yoshida Kenichiro Naito Kimiteru Ito Tatsuya Higashi Hiroaki Kurihara Makoto Ueno Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64 Pharmaceuticals antibody–drug conjugates antibody–chelator conjugates chromatography size exclusion multi-angle light scattering hydrophobic interaction chromatography |
| title | Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64 |
| title_full | Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64 |
| title_fullStr | Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64 |
| title_full_unstemmed | Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64 |
| title_short | Process to Remove the Size Variants Contained in the Antibody–Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64 |
| title_sort | process to remove the size variants contained in the antibody chelator complex pcta ncab001 for radiolabeling with copper 64 |
| topic | antibody–drug conjugates antibody–chelator conjugates chromatography size exclusion multi-angle light scattering hydrophobic interaction chromatography |
| url | https://www.mdpi.com/1424-8247/16/10/1341 |
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