Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer.
Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer.
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多模式成像指导前列腺癌血管靶向的临床前试验。
DOI：
10.18632/oncotarget.4463
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Seshadri M
中科院分区：
文献类型：
--
作者：
Kalmuk J;Folaron M;Buchinger J;Pili R;Seshadri M
与去势抵抗性前列腺癌（CRPC）相关的高死亡率强调了改善该患者人群治疗选择的必要性。本研究的目的是检查血管靶向治疗前列腺癌的潜力。在植入雄性FVB小鼠的皮下和原位Myc-CaP前列腺肿瘤中进行实验研究，以检查新型微管靶向血管破坏剂（VDA）EPC 2407（Crolibulin™）的功效。基于磁共振成像（MRI）、生物发光成像（BLI）和超声（US）的非侵入性多模态成像方法用于指导临床前试验设计和监测肿瘤对治疗的反应。影像学结果与组织病理学评估、肿瘤生长和生存分析相关。对比增强MRI显示EPC 2407对皮下和原位Myc-CaP肿瘤的有效抗血管活性。在雄激素反应元件下表达荧光素酶的Myc-CaP肿瘤（Myc-CaP/ARE-luc）的纵向BLI揭示了AR信号传导的变化和去势后肿瘤内递送精氨酸底物的减少，表明血流减少。通过US和MRI证实了这种血流减少。联合治疗导致持续的血管抑制，抑制肿瘤再生长，并在两种模型中赋予生存益处。这些结果证明了血管靶向结合雄激素剥夺对前列腺癌的治疗潜力。
The high mortality rate associated with castration-resistant prostate cancer (CRPC) underscores the need for improving therapeutic options for this patient population. The purpose of this study was to examine the potential of vascular targeting in prostate cancer. Experimental studies were carried out in subcutaneous and orthotopic Myc-CaP prostate tumors implanted into male FVB mice to examine the efficacy of a novel microtubule targeted vascular disrupting agent (VDA), EPC2407 (Crolibulin™). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to guide preclinical trial design and monitor tumor response to therapy. Imaging results were correlated with histopathologic assessment, tumor growth and survival analysis. Contrast-enhanced MRI revealed potent antivascular activity of EPC2407 against subcutaneous and orthotopic Myc-CaP tumors. Longitudinal BLI of Myc-CaP tumors expressing luciferase under the androgen response element (Myc-CaP/ARE-luc) revealed changes in AR signaling and reduction in intratumoral delivery of luciferin substrate following castration suggestive of reduced blood flow. This reduction in blood flow was validated by US and MRI. Combination treatment resulted in sustained vascular suppression, inhibition of tumor regrowth and conferred a survival benefit in both models. These results demonstrate the therapeutic potential of vascular targeting in combination with androgen deprivation against prostate cancer.
影响因子：
2.6
作者：
Shi J;Yin X;Xu R;Wang Y;Jin L;Gao W
通讯作者：
Gao W