Journal Article Radioimmunotherapy of pancreatic cancer xenografts in nude mice using 90Y-labeled anti-α6β4 integrin antibody.

Winn Aung, U  ,  Tsuji, Atsushi  ,  Sudo, Hitomi  ,  Sugyo, Aya  ,  Ukai, Yoshinori  ,  Kouda, Katsushi  ,  Kurosawa, Yoshikazu  ,  Furukawa, Takako  ,  Saga, Tsuneo

7 ( 25 )  , pp.38835 - 38844 , 2016-05 , Inpact Journals
The contribution of integrin α6β4 (α6β4) overexpression to the pancreaticcancer invasion and metastasis has been previously shown. We have reportedimmunotargeting of α6β4 for radionuclide-based and near-infrared fluorescenceimaging in a pancreatic cancer model. In this study, we prepared yttrium-90 labeledanti-α6β4 antibody (90Y-ITGA6B4) and evaluated its radioimmunotherapeutic efficacyagainst pancreatic cancer xenografts in nude mice. Mice bearing xenograft tumorswere 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) doubleadministrations of unlabeled ITGA6B4 with once-weekly schedule and (5) theuntreated control. Biweekly tumor volume measurements and immunohistochemicalanalyses of tumors at 2 days post-administration were performed to monitor theresponse to treatments. To assess the toxicity, body weight was measured biweekly.Additionally, at 27 days post-administration, blood samples were collected throughcardiac puncture, and hematological parameters, hepatic and renal functions wereanalyzed. Both 90Y-ITGA6B4 treatment groups showed reduction in tumor volumes(P < 0.04), decreased cell proliferation marker Ki-67-positive cells and increasedDNA damage marker p-H2AX-positive cells, compared with the other groups. Micetreated with double administrations of 90Y-ITGA6B4, exhibited myelosuppression.There were no significant differences in hepatic and renal functions between the 2treatment groups and the other groups. Our results suggest that 90Y-ITGA6B4 is apromising radioimmunotherapeutic agent against α6β4 overexpressing tumors. In thefuture studies, dose adjustment for fractionated RIT should be considered carefullyin order to get the optimal effect while avoiding myelotoxicity.

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