@misc{oai:repo.qst.go.jp:00071740, author = {Winn, Aung U and Tsuji, Atsushi and Sudou, Hitomi and Sugyou, Aya and Furukawa, Takako and Ukai, Yoshinori and Kurosawa, Yoshikazu and Saga, Tsuneo and U Winn Aung and 辻 厚至 and 須藤 仁美 and 須尭 綾 and 古川 高子 and 佐賀 恒夫}, month = {Sep}, note = {Background: Pancreatic cancer is a challenging malignancy in term of its less specific symptoms, late diagnosis and limited therapeutic options. There is an urgent need to explore suitable molecular markers and imaging probes to aid in the early and specific detection of pancreatic cancer. Experimental imaging technique targeting to these biomarkers will pave the way toward the development of individualized therapeutic strategies and clinical management. According to the literature, α6β4 integrin is often highly expressed in pancreatic cancer cells, whereas it is hardly expressed in pancreatitis and normal pancreatic cells. Objective: In this study, we proposed the α6β4 integrin as a good target of pancreatic cancer and conducted the two molecular imaging modalities using a fluorophore-labeled or radiolabeled antibody against α6β4, and assessed their potential fescesability for pancreatic cancer imaging in animal model. Materials and Methods: Various level of α6β4 integrin expression in some human pancreatic cancer cell lines was examined with western blotting and flow cytometry. The BxPC-3 cell line which has the high expression of α6β4 was used as a representative, and a mouse cell line A4 was used as its negative counterpart. We labeled the human monoclonal anti-α6β4 integrin antibody with fluorophore Indocyanine green (ICG) or radioisotope 111In-DTPA. After injection of ICG-labeled probe to mice bearing xenografted tumors, in vivo and ex vivo near-infrared imaging (NIR) and fluorescence microscopic examination of tumors were done. In vivo 111In-DTPA-labeled probe biodistribution study, single-photon emission computed tomography (SPECT) imaging, post imaging ex vivo autoradiography and immunohistochemical (IH) studies were also performed. Results: Pancreatic cancer cell lines showed various degree of high α6β4 expression. Integrin α6β4 over-expressing BxPC-3 tumor showed not only the significantly higher fluorescence intensity or radioactivity but also the slower washout of these probes on both NIR imaging and SPECT, respectively, when it was compared to non-target A4 tumor. In vivo biodistribution profile of 111In-labeled probe, autoradiography and IH examination confirmed the α6β4 specific binding of probe. Conclusion: Here, we could suggest that α6β4 integrin is a desirable target for the diagnosis of pancreatic cancer and it could be detected by NIR imaging and nuclear imaging via ICG-labeled or radiolabeled antibody against α6β4., The World Molecular Imaging Congress 2014 (WMIC 2014) に参加}, title = {Integrin α6β4-targeted near-infrared imaging and single-photon emission computed tomography in a pancreatic cancer model}, year = {2014} }