坏死
纤维蛋白样坏死
病理
医学
水肿
抗体
免疫学
内科学
血管炎
疾病
作者
Xiaoyu Jiang,John A. Engelbach,Yuan Lu,Jeremy Cates,Feng Gao,Robert E. Drzymala,Dennis E. Hallahan,Keith M. Rich,Robert E. Schmidt,Joseph J. H. Ackerman,Joel R. Garbow
标识
DOI:10.1158/1078-0432.ccr-13-1941
摘要
Abstract Purpose: To quantify the effectiveness of anti-VEGF antibodies (bevacizumab and B20-4.1.1) as mitigators of radiation-induced, central nervous system (brain) necrosis in a mouse model. Experimental Design: Cohorts of mice were irradiated with single-fraction 50- or 60-Gy doses of radiation targeted to the left hemisphere (brain) using the Leksell Perfexion Gamma Knife. The onset and progression of radiation necrosis were monitored longitudinally by in vivo, small-animal MRI, beginning 4 weeks after irradiation. MRI-derived necrotic volumes for antibody (Ab)-treated and untreated mice were compared. MRI results were supported by correlative histology. Results: Hematoxylin and eosin–stained sections of brains from irradiated, non–Ab-treated mice confirmed profound tissue damage, including regions of fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, loss of neurons, and edema. Treatment with the murine anti-VEGF antibody B20-4.1.1 mitigated radiation-induced changes in an extraordinary, highly statistically significant manner. The development of radiation necrosis in mice under treatment with bevacizumab (a humanized anti-VEGF antibody) was intermediate between that for B20-4.1.1–treated and non–Ab-treated animals. MRI findings were validated by histologic assessment, which confirmed that anti-VEGF antibody treatment dramatically reduced late-onset necrosis in irradiated brain. Conclusions: The single-hemispheric irradiation mouse model, with longitudinal MRI monitoring, provides a powerful platform for studying the onset and progression of radiation necrosis and for developing and testing new therapies. The observation that anti-VEGF antibodies are effective mitigants of necrosis in our mouse model will enable a wide variety of studies aimed at dose optimization and timing and mechanism of action with direct relevance to ongoing clinical trials of bevacizumab as a treatment for radiation necrosis. Clin Cancer Res; 20(10); 2695–702. ©2014 AACR.
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