A Novel PET Imaging Using 64Cu-Labeled Monoclonal Antibody against Mesothelin Commonly Expressed on Cancer CellsReport as inadecuate




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Journal of Immunology Research - Volume 2015 2015, Article ID 268172, 15 pages -

Research Article

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan

Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan

Collaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan

Department of Research and Development, Ina Institute, Medical & Biological Laboratories, Co., Ltd., Ina 396-0002, Japan

Technology Research Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan

Received 26 November 2014; Revised 14 February 2015; Accepted 19 February 2015

Academic Editor: Peirong Jiao

Copyright © 2015 Kazuko Kobayashi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mesothelin MSLN is a 40-kDa cell differentiation-associated glycoprotein appearing with carcinogenesis and is highly expressed in many human cancers, including the majority of pancreatic adenocarcinomas, ovarian cancers, and mesotheliomas, while its expression in normal tissue is limited to mesothelial cells lining the pleura, pericardium, and peritoneum. Clone 11-25 is a murine hybridoma secreting monoclonal antibody mAb against human MSLN. In this study, we applied the 11-25 mAb to in vivo imaging to detect MSLN-expressing tumors. In in vitro and ex vivo immunochemical studies, we demonstrated specificity of 11-25 mAb to membranous MSLN expressed on several pancreatic cancer cells. We showed the accumulation of Alexa Fluor 750-labeled 11-25 mAb in MSLN-expressing tumor xenografts in athymic nude mice. Then, 11-25 mAb was labeled with

Cu via a chelating agent DOTA and was used in both in vitro cell binding assay and in vivo positron emission tomography PET imaging in the tumor-bearing mice. We confirmed that

Cu-labeled 11-25 mAb highly accumulated in MSLN-expressing tumors as compared to MSLN-negative ones. The

Cu-labeled 11-25 mAb is potentially useful as a PET probe capable of being used for wide range of tumors, rather than

F-FDG that occasionally provides nonspecific accumulation into the inflammatory lesions.





Author: Kazuko Kobayashi, Takanori Sasaki, Fumiaki Takenaka, Hiromasa Yakushiji, Yoshihiro Fujii, Yoshiro Kishi, Shoichi Kita, Lian

Source: https://www.hindawi.com/



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