@misc{oai:repo.qst.go.jp:00072996, author = {U, Winn Aung and Tsuji, Atsushi and Sugyo, Aya and Sudo, Hitomi and Takashima, Hiroki and Yasunaga, Masahiro and Matsumura, Yasuhiro and Higashi, Tatsuya and U Winn Aung and 辻 厚至 and 須尭 綾 and 須藤 仁美 and 東 達也}, month = {Oct}, note = {Purpose: Tissue Factor (TF) is a transmembrane protein and its overexpression is associated with increased tumor growth, tumor angiogenesis and metastatic potential in many malignancies, including pancreatic cancer. Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer treatment that enables highly selective cell death after systemic administration of a photosensitizer-antibody conjugate followed by subsequent NIR light exposure. In this study, we describe the photoimmunotherapeutic effect induced by a rat IgG2b anti-TF monoclonal antibody (anti-TF mAb), conjugated to the photosensitizer, Indocyanine green (ICG), in a TF-expressing BxPC-3 pancreatic cancer model. Materials and methods: Specific binding of the anti-TF-ICG antibody to the TF-expressing BxPC-3 pancreatic cancer cell line was examined by fluorescence microscopy. NIR-PIT-induced cell death was determined by using cell viability imaging assay after exposure of the cells to NIR light. Anti-TF-ICG antibody accumulation in xenograft tumor was acquired in in vivo longitudinal fluorescence imaging. To conduct NIR-PIT, tumor-bearing mice were separated into 5 groups: (1) 100 μg of anti- TF-ICG i.v. administration followed by NIR light exposure (50 J/cm2) for two consecutive days (Day 1 and 2); (2) NIR light exposure (50 J/cm2) only for two consecutive days (Day 1 and 2); (3) 100 μg of anti-TF-ICG i.v. administration; (4) 100 μg of unlabeled anti-TF i.v. administration; (5) the untreated control. Biweekly tumor volume measurements, histopathological and immunohistochemical (IHC) analyses of tumors at 3 days post-administration of anti-TF-ICG antibody were performed to monitor the effect of treatments. Results: Dead cells were obviously seen with cell viability imaging assay. Tumor growth was significantly inhibited by NIR-PIT compared with the other control groups (P < 0.01) for 27 days. Tumors received NIR-PIT showed the evidence of necrotic cell death associated features on H&E staining and decreased cell proliferation marker Ki-67-positive cells on IHC examination. Conclusion: The anti-TF-ICG antibody is suitable as a photosensitizer-antibody conjugate for NIR-PIT. Furthermore, NIR-PIT with the anti-TF-ICG antibody conjugate promises to open a new avenue for treatment of TF-expressing pancreatic cancer and that could be ultimately applicable in clinical use., Annual Congress of the European Association of Nuclear Medicine 2018}, title = {Near-infrared Photoimmunotherapy Targeting Pancreatic Cancer With Tissue Factor Antibody}, year = {2018} }