Characterization and Stabilization of a New 64Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography

Matsumoto, Hiroki and Igarashi, Chika and Tachibana, Tomoko and Hihara, Fukiko and Waki, Atsuo and Zhang, Ming-Rong and Yoshida, Sei and Naito, Kenichiro and Kurihara, Hiroaki and Ueno, Makoto and Ito, Kimiteru and Higashi, Tatsuya and Yoshii, Yukie (2021) Characterization and Stabilization of a New 64Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography. Pharmaceutics, 14 (1). p. 67. ISSN 1999-4923

[thumbnail of pharmaceutics-14-00067-v2.pdf] Text
pharmaceutics-14-00067-v2.pdf - Published Version

Download (1MB)

Abstract

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 64Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called 64Cu-NCAB001 ipPET. Generally, in clinical research, a radiometal-antibody complex must be prepared immediately before use at the imaging site. To make 64Cu-NCAB001 ipPET available to daily clinical practices in a sustainable way, the NCAB001-chelator conjugate and 64Cu-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 64Cu-NCAB001, we developed a new formulation to stabilize PCTA-NCAB001 and 64Cu-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 64Cu-NCAB001 for up to 24 h after radiolabeling with a sufficient radioactivity concentration for clinical use. These results may accelerate the future use of 64Cu-NCAB001 ipPET in clinical settings for the early diagnosis and treatment of pancreatic cancer.

Item Type: Article
Uncontrolled Keywords: 64Cu-NCAB001; ipPET; process development; stability; radiometal-antibody complex
Subjects: Euro Archives > Medical Science
Depositing User: Managing Editor
Date Deposited: 12 Nov 2022 05:01
Last Modified: 18 Sep 2023 04:27
URI: http://publish7promo.com/id/eprint/113

Actions (login required)

View Item
View Item