量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Mesothelioma is an aggressive tumor arising from serosal surfaces of the pleura and peritoneum closely related to asbestos exposure. This is a rare tumor, but the incidence is increasing worldwide over the next several decades because of high consumption of asbestos. Although the prognosis of patients with current treatments remains poor, that of patients at an early stage has been reported to be improved. Thus, the diagnosis at the early stage of mesothelioma is necessary for the better prognosis. However, current diagnostic modalities including FDG-PET are difficult to detect the early stage of mesothelioma, and it is essential to develop a new diagnostic method for detection at the early stage. The ERC/Mesothelin (ERC) is a cell surface glycoprotein and is strongly expressed in epithelioid subtype of mesothelioma. The primary product of ERC is a 71-kDa precursor protein, which is cleaved into a 40-kDa C-terminal fragment that remains membrane-bound and a 31-kDa N-terminal fragment that is secreted into the blood. Since the antibody against the C-terminal fragment is very useful for distinguishing pleural mesotheliomas from adenocarcinomas and squamous cell carcinomas of the lung by immunohistochemistry, the radiolabeled antibody recognizing C-terminal fragment could be used for in vivo imaging of ERC-positive mesotheliomas. In this study, we radiolabeled anti-ERC antibody with 125I and 111In, and performed cell binding, competitive inhibition and internalization assays in vitro using a human mesothelioma cell line, H226, highly expressing ERC primarily localized to the cell membrane. We also performed biodistribution and SPECT imaging in vivo using tumor-bearing mice. These results showed that the radiolabeled antibody specifically bound to ERC expressing cells and were weakly internalized, and the 111In-labeled antibody highly accumulated in the xenografted tumor, which was readily visualized by SPECT. The radiolabeled anti-ERC antibody would be useful for the PET/SPECT imaging of malignant mesothelioma.
Development of anti-ERC/mesothelin antibody probe for PET/SPECT imaging of Malignant Mesothelioma
