@article{oai:repo.qst.go.jp:00046980, author = {Sugyou, Aya and Tsuji, Atsushi and Sudo, Hitomi and Nagatsu, Koutarou and Koizumi, Mitsuru and Zhang, Ming-Rong and Saga, Tsuneo and et.al and 須尭 綾 and 辻 厚至 and 須藤 仁美 and 永津 弘太郎 and 小泉 満 and 張 明栄 and 佐賀 恒夫}, issue = {4}, journal = {PLoS ONE (Online only:URL:http://www.plosone.org)}, month = {Apr}, note = {INTRODUCTION: \nPancreatic cancer is an aggressive cancer and its prognosis remains poor. Therefore, additional effective therapy is required to augment and/or complement current therapy. CD147, high expression in pancreatic cancer, is involved in the metastatic process and is considered a good candidate for targeted therapy. CD147-specfic imaging could be useful for selection of appropriate patients. Therefore, we evaluated the potential of a fully human anti-CD147 monoclonal antibody 059-053 as a new positron emission tomography (PET) probe for pancreatic cancer. \nMETHODS: \nCD147 expression was evaluated in four pancreatic cancer cell lines (MIA Paca-2, PANC-1, BxPC-3, and AsPC-1) and a mouse cell line A4 as a negative control. Cell binding, competitive inhibition and internalization assays were conducted with (125)I-, (67)Ga-, or (89)Zr-labeled 059-053. In vivo biodistribution of (125)I- or (89)Zr-labeled 059-053 was conducted in mice bearing MIA Paca-2 and A4 tumors. PET imaging with [(89)Zr]059-053 was conducted in subcutaneous and orthotopic tumor mouse models. \nRESULTS: \nAmong four pancreatic cancer cell lines, MIA Paca-2 cells showed the highest expression of CD147, while A4 cells had no expression. Immunohistochemical staining showed that MIA Paca-2 xenografts also highly expressed CD147 in vivo. Radiolabeled 059-053 specifically bound to MIA Paca-2 cells with high affinity, but not to A4. [(89)Zr]059-053 uptake in MIA Paca-2 tumors increased with time from 11.0+-1.3% injected dose per gram (ID/g) at day 1 to 16.9+-3.2% ID/g at day 6, while [(125)I]059-053 uptake was relatively low and decreased with time, suggesting that 059-053 was internalized into tumor cells in vivo and (125)I was released from the cells. PET with [(89)Zr]059-053 clearly visualized subcutaneous and orthotopic tumors. \nCONCLUSION: \n[(89)Zr]059-053 is a promising PET probe for imaging CD147 expression in pancreatic cancer and has the potential to select appropriate patients with CD147-expressing tumors who could gain benefit from anti-CD147 therapy.}, pages = {e61230--e61230}, title = {Evaluation of (89)Zr-Labeled Human Anti-CD147 Monoclonal Antibody as a Positron Emission Tomography Probe in a Mouse Model of Pancreatic Cancer.}, volume = {8}, year = {2013} }