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Evaluation of 64Cu-labeled new anti-EGFR antibody NCAB001 with intraperitoneal injection for early PET diagnosis of pancreatic cancer in orthotopic tumor-xenografted mice and nonhuman primates
https://repo.qst.go.jp/records/84083
https://repo.qst.go.jp/records/8408352be55e2-67d1-4d6b-9c19-1c302ab633e7
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-09-22 | |||||
| タイトル | ||||||
| タイトル | Evaluation of 64Cu-labeled new anti-EGFR antibody NCAB001 with intraperitoneal injection for early PET diagnosis of pancreatic cancer in orthotopic tumor-xenografted mice and nonhuman primates | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Hiroki, Matsumoto
× Hiroki, Matsumoto× Tadashi , Watabe× Chika, Igarashi× Tomoko, Tachibana× Fukiko, Hihara× Atsuo, Waki× Zhang, Ming-Rong× Hideaki, Tashima× Taiga, Yamaya× Kazuhiro , Ooe× Eku , Shimosegawa× Jun, Hatazawa× Sei , Yoshida× Kenichiro, Naito× Hiroaki, Kurihara× Makoto, Ueno× Kimiteru, Ito× Tatsuya, Higashi× Yukie, Yoshii× Hiroki, Matsumoto× Chika, Igarashi× Tomoko, Tachibana× Fukiko, Hihara× Atsuo, Waki× Zhang, Ming-Rong× Hideaki, Tashima× Taiga, Yamaya× Tatsuya, Higashi× Yukie, Yoshii |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Pancreatic cancer has a poor prognosis because early diagnosis is challenging. We recently reported a new approach for detecting very small tumor lesions in the pancreas (≥3 mm) by positron emission tomography (PET) using an intraperitoneally (ip)-administrated anti-epidermal growth factor receptor (EGFR) antibody (cetuximab) labeled with 64Cu, called 64Cu-cetuximab ipPET, in orthotopic pancreatic tumor-xenografted mice. For translation of this approach to clinical practice, we established an efficient and sustainable production of NCAB001, a new anti-EGFR antibody, and conducted a preclinical evaluation of 64Cu-NCAB001 in the pancreatic cancer mouse model described above, and in non-human primates. Methods: NCAB001 was manufactured under cGMP conditions. The radiochemical and biological properties of 64Cu-NCAB001 were evaluated and compared with our previous data and with clinically available cetuximab (Erbitux). Tumor uptake in orthotopic pancreatic tumor xenografted mice was also evaluated. Pharmacokinetics and radiation dosimetry were examined using PET images acquired after the ip administration of 64Cu-NCAB001 into cynomolgus monkeys with pharmacologic safety monitoring. Results: Radio-chromatography, cell binding assays, biodistribution, and tumor uptake of 64Cu-NCAB001 in mice were identical to those of 64Cu-cetuximab. The ip administration of 64Cu-NCAB001 into monkeys was safely conducted using ultrasound imaging. PET images in monkeys showed that ip-administered 64Cu-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, suggesting that the background activities around the pancreatic cancer can be expected to be negligible in patients in future clinical studies. The liver received a relatively high human-estimated radiation-absorbed dose among the individual organs (0.107 mSv/MBq). The estimated effective dose was 0.0174 mSv/MBq. These results indicate that 130 MBq/injection is acceptable as the starting dose for our planned first-in-patient clinical trial of 64Cu-NCAB001 ipPET. Conclusion: The feasibility of 64Cu-NCAB001 ipPET was demonstrated in a mouse model of small orthotopic tumors and non-human primates. Our data support the initiation of clinical trials of 64Cu-NCAB001 ipPET to transfer this promising tool for the early diagnosis of pancreatic cancers in clinical practice. | |||||
| 書誌情報 |
Pharmaceuticals 巻 14, 号 10, p. 950, 発行日 2021-09 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1424-8247 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.3390/ph14100950 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.mdpi.com/1424-8247/14/10/950 | |||||
