RT Journal Article
SR Electronic
T1 Integrin α<sub>v</sub>β<sub>3</sub>-Targeted Radioimmunotherapy of Glioblastoma Multiforme
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 7330
OP 7339
DO 10.1158/1078-0432.CCR-08-0797
VO 14
IS 22
A1 Veeravagu, Anand
A1 Liu, Zhaofei
A1 Niu, Gang
A1 Chen, Kai
A1 Jia, Bing
A1 Cai, Weibo
A1 Jin, Cunjing
A1 Hsu, Andrew R.
A1 Connolly, Andrew J.
A1 Tse, Victor
A1 Wang, Fan
A1 Chen, Xiaoyuan
YR 2008
UL http://clincancerres.aacrjournals.org/content/14/22/7330.abstract
AB Purpose: Abegrin is a monoclonal antibody to human integrin αVβ3, a cell adhesion molecule highly expressed on actively angiogenic endothelium and glioblastoma multiforme tumor cells. The purpose of this study was to evaluate the efficacy of a novel 90Y-Abegrin radioimmunotherapeutic agent in murine xenograft glioblastoma models with noninvasive in vivo molecular imaging modalities. Experimental Design: A s.c. U87MG human glioblastoma xenograft model was used to determine maximum tolerated dose (MTD), biodistribution, dose response, and efficacy of 90Y-Abegrin. Antitumor efficacy was also characterized in an orthotopic U87MG and in a HT-29 colorectal cancer model, a low integrin-expressing carcinoma. Small-animal positron emission tomography imaging was used to correlate histologic findings of treatment efficacy. Results: MTD and dose response analysis revealed 200 μCi per mouse as appropriate treatment dose with hepatic clearance and no organ toxicity. 90Y-Abegrin–treated U87MG tumor mice showed partial regression of tumor volume, with increased tumor volumes in 90Y-IgG, Abegrin, and saline groups. 18F-FDG imaging revealed a reduction of cell proliferation and metabolic activity whereas 18F-FLT reflected decreased DNA synthesis in the 90Y-Abegrin group. Ki67 analysis showed reduced proliferative index and quantitative terminal deoxynucleotidyl transferase dUTP nick-end labeling–positive analysis revealed increased DNA fragmentation and apoptosis in 90Y-Abegrin animals. CD31 and 4′,6-diamidino-2-phenylindole staining showed increased vascular fragmentation and dysmorphic vessel structure in 90Y-Abegrin animals only. Orthotopic U87MG tumors treated with 90Y-Abegrin displayed reduced tumor volume. HT-29 tumors showed no significant difference among the various groups. Conclusion: Radioimmunotherapy with 90Y-labeled Abegrin may prove promising in the treatment of highly vascular, invasive, and heterogeneous malignant brain tumors.