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

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.

Number of accesses :  

Other information