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Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography
Early diagnosis of pancreatic cancer using current imaging modalities remains challenging. We have developed a new approach to identify tumor lesions ≥ 3 mm in the pancreas by positron emission tomography (PET) with a new intraperitoneally administered (64)Cu-labeled anti-epidermal growth factor rec...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779674/ https://www.ncbi.nlm.nih.gov/pubmed/35056963 http://dx.doi.org/10.3390/pharmaceutics14010067 |
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author | Matsumoto, Hiroki Igarashi, Chika Tachibana, Tomoko Hihara, Fukiko Waki, Atsuo Zhang, Ming-Rong Yoshida, Sei Naito, Kenichiro Kurihara, Hiroaki Ueno, Makoto Ito, Kimiteru Higashi, Tatsuya Yoshii, Yukie |
author_facet | Matsumoto, Hiroki Igarashi, Chika Tachibana, Tomoko Hihara, Fukiko Waki, Atsuo Zhang, Ming-Rong Yoshida, Sei Naito, Kenichiro Kurihara, Hiroaki Ueno, Makoto Ito, Kimiteru Higashi, Tatsuya Yoshii, Yukie |
author_sort | Matsumoto, Hiroki |
collection | PubMed |
description | Early diagnosis of pancreatic cancer using current imaging modalities remains challenging. We have developed a new approach to identify tumor lesions ≥ 3 mm in the pancreas by positron emission tomography (PET) with a new intraperitoneally administered (64)Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called (64)Cu-NCAB001 ipPET. Generally, in clinical research, a radiometal-antibody complex must be prepared immediately before use at the imaging site. To make (64)Cu-NCAB001 ipPET available to daily clinical practices in a sustainable way, the NCAB001-chelator conjugate and (64)Cu-NCAB001 must be characterized and stabilized. NCAB001 was manufactured under cGMP conditions. NCAB001 was conjugated with a bifunctional chelator (p-SCN-Bn-PCTA), and the antibody-chelator conjugate (PCTA-NCAB001) was characterized by LC/MS and ELISA. Thereafter, to effectively manufacture (64)Cu-NCAB001, we developed a new formulation to stabilize PCTA-NCAB001 and (64)Cu-NCAB001. An average of three PCTA chelators were conjugated per molecule of NCAB001. The relative binding potency of PCTA-NCAB001 was comparable to cetuximab. The formulation consisting of acetate buffer, glycine, and polysorbate-80 stabilized PCTA-NCAB001 for a year-long storage. Additionally, this formulation enabled the stabilization of (64)Cu-NCAB001 for up to 24 h after radiolabeling with a sufficient radioactivity concentration for clinical use. These results may accelerate the future use of (64)Cu-NCAB001 ipPET in clinical settings for the early diagnosis and treatment of pancreatic cancer. |
format | Online Article Text |
id | pubmed-8779674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87796742022-01-22 Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography Matsumoto, Hiroki Igarashi, Chika Tachibana, Tomoko Hihara, Fukiko Waki, Atsuo Zhang, Ming-Rong Yoshida, Sei Naito, Kenichiro Kurihara, Hiroaki Ueno, Makoto Ito, Kimiteru Higashi, Tatsuya Yoshii, Yukie Pharmaceutics Article Early diagnosis of pancreatic cancer using current imaging modalities remains challenging. We have developed a new approach to identify tumor lesions ≥ 3 mm in the pancreas by positron emission tomography (PET) with a new intraperitoneally administered (64)Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called (64)Cu-NCAB001 ipPET. Generally, in clinical research, a radiometal-antibody complex must be prepared immediately before use at the imaging site. To make (64)Cu-NCAB001 ipPET available to daily clinical practices in a sustainable way, the NCAB001-chelator conjugate and (64)Cu-NCAB001 must be characterized and stabilized. NCAB001 was manufactured under cGMP conditions. NCAB001 was conjugated with a bifunctional chelator (p-SCN-Bn-PCTA), and the antibody-chelator conjugate (PCTA-NCAB001) was characterized by LC/MS and ELISA. Thereafter, to effectively manufacture (64)Cu-NCAB001, we developed a new formulation to stabilize PCTA-NCAB001 and (64)Cu-NCAB001. An average of three PCTA chelators were conjugated per molecule of NCAB001. The relative binding potency of PCTA-NCAB001 was comparable to cetuximab. The formulation consisting of acetate buffer, glycine, and polysorbate-80 stabilized PCTA-NCAB001 for a year-long storage. Additionally, this formulation enabled the stabilization of (64)Cu-NCAB001 for up to 24 h after radiolabeling with a sufficient radioactivity concentration for clinical use. These results may accelerate the future use of (64)Cu-NCAB001 ipPET in clinical settings for the early diagnosis and treatment of pancreatic cancer. MDPI 2021-12-28 /pmc/articles/PMC8779674/ /pubmed/35056963 http://dx.doi.org/10.3390/pharmaceutics14010067 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Matsumoto, Hiroki Igarashi, Chika Tachibana, Tomoko Hihara, Fukiko Waki, Atsuo Zhang, Ming-Rong Yoshida, Sei Naito, Kenichiro Kurihara, Hiroaki Ueno, Makoto Ito, Kimiteru Higashi, Tatsuya Yoshii, Yukie Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography |
title | Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography |
title_full | Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography |
title_fullStr | Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography |
title_full_unstemmed | Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography |
title_short | Characterization and Stabilization of a New (64)Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography |
title_sort | characterization and stabilization of a new (64)cu-labeled anti-egfr antibody ncab001 for the early detection of pancreatic cancer with positron emission tomography |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779674/ https://www.ncbi.nlm.nih.gov/pubmed/35056963 http://dx.doi.org/10.3390/pharmaceutics14010067 |
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