@article{oai:repo.qst.go.jp:00049467,
 author = {Ｕ, Ｗｉｎｎ Ａｕｎｇ and Tsuji, Atsushi and Sudo, Hitomi and Sugyo, Aya and Ukai, Yoshinori and Kouda, Katsushi and Kurosawa, Yoshikazu and Furukawa, Takako 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},
 issue = {25},
 journal = {Oncotarget},
 month = {Jun},
 note = {The contribution of integrin α6β4 (α6β4) overexpression to the pancreatic
cancer invasion and metastasis has been previously shown. We have reported
immunotargeting of α6β4 for radionuclide-based and near-infrared fluorescence
imaging in a pancreatic cancer model. In this study, we prepared yttrium-90 labeled
anti-α6β4 antibody (90Y-ITGA6B4) and evaluated its radioimmunotherapeutic efficacy
against pancreatic cancer xenografts in nude mice. Mice bearing xenograft tumors
were randomly divided into 5 groups: (1) single administration of 90Y-ITGA6B4
(3.7MBq), (2) double administrations of 90Y-ITGA6B4 with once-weekly schedule
(3.7MBq x 2), (3) single administration of unlabeled ITGA6B4, (4) double
administrations of unlabeled ITGA6B4 with once-weekly schedule and (5) the
untreated control. Biweekly tumor volume measurements and immunohistochemical
analyses of tumors at 2 days post-administration were performed to monitor the
response to treatments. To assess the toxicity, body weight was measured biweekly.
Additionally, at 27 days post-administration, blood samples were collected through
cardiac puncture, and hematological parameters, hepatic and renal functions were
analyzed. Both 90Y-ITGA6B4 treatment groups showed reduction in tumor volumes
(P < 0.04), decreased cell proliferation marker Ki-67-positive cells and increased
DNA damage marker p-H2AX-positive cells, compared with the other groups. Mice
treated with double administrations of 90Y-ITGA6B4, exhibited myelosuppression.
There were no significant differences in hepatic and renal functions between the 2
treatment groups and the other groups. Our results suggest that 90Y-ITGA6B4 is a
promising radioimmunotherapeutic agent against α6β4 overexpressing tumors. In the
future studies, dose adjustment for fractionated RIT should be considered carefully
in order to get the optimal effect while avoiding myelotoxicity.},
 pages = {38835--38844},
 title = {Radioimmunotherapy of pancreatic cancer xenografts in nude mice using 90Y-labeled anti-α6β4 integrin antibody.},
 volume = {7},
 year = {2016}
}