Multimodal imaging guided preclinical trials of vascular targeting in XXXX .

@entity1 @entity263 @entity19 @entity5 @entity10051 @entity342 @entity73242
The high mortality rate associated with @entity263 ( @entity263 ) underscores the need for improving therapeutic options for this @entity1 population. The purpose of this study was to examine the potential of vascular targeting in @entity263 . Experimental studies were carried out in subcutaneous and orthotopic Myc-CaP @entity263 implanted into male FVB @entity19 to examine the efficacy of a novel microtubule targeted vascular disrupting agent (VDA), EPC2407 ( @entity73242   ). 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 @entity5 response to therapy. Imaging results were correlated with histopathologic assessment, @entity5 growth and survival analysis. Contrast-enhanced MRI revealed potent antivascular activity of EPC2407 against @entity5 . Longitudinal BLI of Myc-CaP @entity5 expressing luciferase under the @entity342 response element (Myc-CaP/ARE-luc) revealed changes in AR signaling and reduction in intratumoral delivery of @entity10051 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 @entity5 regrowth and conferred a survival benefit in both models. These results demonstrate the therapeutic potential of vascular targeting in combination with @entity342 deprivation against @entity263 .
