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Evaluation of (64)Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates
Objectives: To improve the prognosis of pancreatic cancer, new imaging methods to identify tumor lesions at a size of <1 cm are urgently needed. To approach this clinical issue, we developed a new method to detect small tumor lesions in the pancreas (≥3 mm) by positron emission tomography (PET) u...
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/PMC8540406/ https://www.ncbi.nlm.nih.gov/pubmed/34681174 http://dx.doi.org/10.3390/ph14100950 |
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author | Matsumoto, Hiroki Watabe, Tadashi Igarashi, Chika Tachibana, Tomoko Hihara, Fukiko Waki, Atsuo Zhang, Ming-Rong Tashima, Hideaki Yamaya, Taiga Ooe, Kazuhiro Shimosegawa, Eku Hatazawa, Jun Yoshida, Sei Naito, Kenichiro Kurihara, Hiroaki Ueno, Makoto Ito, Kimiteru Higashi, Tatsuya Yoshii, Yukie |
author_facet | Matsumoto, Hiroki Watabe, Tadashi Igarashi, Chika Tachibana, Tomoko Hihara, Fukiko Waki, Atsuo Zhang, Ming-Rong Tashima, Hideaki Yamaya, Taiga Ooe, Kazuhiro Shimosegawa, Eku Hatazawa, Jun Yoshida, Sei Naito, Kenichiro Kurihara, Hiroaki Ueno, Makoto Ito, Kimiteru Higashi, Tatsuya Yoshii, Yukie |
author_sort | Matsumoto, Hiroki |
collection | PubMed |
description | Objectives: To improve the prognosis of pancreatic cancer, new imaging methods to identify tumor lesions at a size of <1 cm are urgently needed. To approach this clinical issue, we developed a new method to detect small tumor lesions in the pancreas (≥3 mm) by positron emission tomography (PET) using an intraperitoneally (ip)-administered (64)Cu-labeled new anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called (64)Cu-NCAB001 ipPET. Methods: NCAB001 was manufactured under cGMP conditions and labeled with (64)Cu. The radiochemical and biological properties of (64)Cu-NCAB001 were evaluated. Tumor uptake of an ip-administered (64)Cu-NCAB001 in mice with orthotopic pancreatic tumor xPA1-DC xenografts was also evaluated. Pharmacokinetics and radiation dosimetry were examined using PET images acquired after the ip administration of (64)Cu-NCAB001 into cynomolgus monkeys with pharmacologic safety monitoring. Results: Radio-chromatography, cell-binding assays, and biodistribution of (64)Cu-NCAB001 in mice were identical to those of our previous data with clinically available cetuximab. Small tumor lesions in the pancreas (≥3 mm) of mice could be identified by (64)Cu-NCAB001 ipPET. The ip administration of (64)Cu-NCAB001 into monkeys was safely conducted using ultrasound imaging. PET images in monkeys showed that ip-administered (64)Cu-NCAB001 was distributed throughout the intraperitoneal cavity for up to 6 h and cleared thereafter. Most of the radioactivity was distributed in the liver and the large intestine. The radioactivity around the pancreas became negligible 24 h after administration. The estimated human effective dose was 0.0174 mSv/MBq. Conclusion: Our data support the initiation of clinical trials of (64)Cu-NCAB001 ipPET to transfer this promising tool for the early diagnosis of pancreatic cancers. |
format | Online Article Text |
id | pubmed-8540406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85404062021-10-24 Evaluation of (64)Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates Matsumoto, Hiroki Watabe, Tadashi Igarashi, Chika Tachibana, Tomoko Hihara, Fukiko Waki, Atsuo Zhang, Ming-Rong Tashima, Hideaki Yamaya, Taiga Ooe, Kazuhiro Shimosegawa, Eku Hatazawa, Jun Yoshida, Sei Naito, Kenichiro Kurihara, Hiroaki Ueno, Makoto Ito, Kimiteru Higashi, Tatsuya Yoshii, Yukie Pharmaceuticals (Basel) Article Objectives: To improve the prognosis of pancreatic cancer, new imaging methods to identify tumor lesions at a size of <1 cm are urgently needed. To approach this clinical issue, we developed a new method to detect small tumor lesions in the pancreas (≥3 mm) by positron emission tomography (PET) using an intraperitoneally (ip)-administered (64)Cu-labeled new anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called (64)Cu-NCAB001 ipPET. Methods: NCAB001 was manufactured under cGMP conditions and labeled with (64)Cu. The radiochemical and biological properties of (64)Cu-NCAB001 were evaluated. Tumor uptake of an ip-administered (64)Cu-NCAB001 in mice with orthotopic pancreatic tumor xPA1-DC xenografts was also evaluated. Pharmacokinetics and radiation dosimetry were examined using PET images acquired after the ip administration of (64)Cu-NCAB001 into cynomolgus monkeys with pharmacologic safety monitoring. Results: Radio-chromatography, cell-binding assays, and biodistribution of (64)Cu-NCAB001 in mice were identical to those of our previous data with clinically available cetuximab. Small tumor lesions in the pancreas (≥3 mm) of mice could be identified by (64)Cu-NCAB001 ipPET. The ip administration of (64)Cu-NCAB001 into monkeys was safely conducted using ultrasound imaging. PET images in monkeys showed that ip-administered (64)Cu-NCAB001 was distributed throughout the intraperitoneal cavity for up to 6 h and cleared thereafter. Most of the radioactivity was distributed in the liver and the large intestine. The radioactivity around the pancreas became negligible 24 h after administration. The estimated human effective dose was 0.0174 mSv/MBq. Conclusion: Our data support the initiation of clinical trials of (64)Cu-NCAB001 ipPET to transfer this promising tool for the early diagnosis of pancreatic cancers. MDPI 2021-09-23 /pmc/articles/PMC8540406/ /pubmed/34681174 http://dx.doi.org/10.3390/ph14100950 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 Watabe, Tadashi Igarashi, Chika Tachibana, Tomoko Hihara, Fukiko Waki, Atsuo Zhang, Ming-Rong Tashima, Hideaki Yamaya, Taiga Ooe, Kazuhiro Shimosegawa, Eku Hatazawa, Jun Yoshida, Sei Naito, Kenichiro Kurihara, Hiroaki Ueno, Makoto Ito, Kimiteru Higashi, Tatsuya Yoshii, Yukie Evaluation of (64)Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates |
title | Evaluation of (64)Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates |
title_full | Evaluation of (64)Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates |
title_fullStr | Evaluation of (64)Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates |
title_full_unstemmed | Evaluation of (64)Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates |
title_short | Evaluation of (64)Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates |
title_sort | evaluation of (64)cu-labeled new anti-egfr antibody ncab001 with intraperitoneal injection for early pet diagnosis of pancreatic cancer in orthotopic tumor-xenografted mice and nonhuman primates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540406/ https://www.ncbi.nlm.nih.gov/pubmed/34681174 http://dx.doi.org/10.3390/ph14100950 |
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