title: A novel PET imaging using ⁶⁴Cu-labeled monoclonal antibody against mesothelin commonly expressed on cancer cells.
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 (64)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 (64)Cu-labeled 11-25 mAb highly accumulated in MSLN-expressing tumors as compared to MSLN-negative ones. The (64)Cu-labeled 11-25 mAb is potentially useful as a PET probe capable of being used for wide range of tumors, rather than (18)F-FDG that occasionally provides nonspecific accumulation into the inflammatory lesions.
authors.affiliation: 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.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Collaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Collaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Takenaka
authors.affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yakushiji
authors.affiliation: Department of Research and Development, Ina Institute, Medical & Biological Laboratories, Co., Ltd., Ina 396-0002, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Research and Development, Ina Institute, Medical & Biological Laboratories, Co., Ltd., Ina 396-0002, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kishi
authors.affiliation: Department of Research and Development, Ina Institute, Medical & Biological Laboratories, Co., Ltd., Ina 396-0002, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kita
authors.affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan ; Technology Research Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.affiliation: Department of Cell Chemistry, 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.
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000000981:diagnostic imaging*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D045744:Cell Line, Tumor; D003300:Copper; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D008297:Male; D000090204:Mesothelin; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; C000715528:Msln protein, mouse; D011868:Radioisotopes; D003300:Copper; D000090204:Mesothelin