Monitoring the treatment efficacy of the vascular disrupting agent CA4P

The purpose of this study was to investigate two non-invasive methods for determining the treatment efficacy of the vascular disrupting agent (VDA) CA4P: gadolinium enhanced dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for perfusion analysis and enzyme-linked immunosorbent assay (ELISA) of blood samples. Candidate proteins were identified by multi-analyte profile analysis of plasma from KHT sarcoma-bearing C3H/HeJ mice after CA4P administration. Candidate proteins were further analysed by ELISA of plasma from treated C3H/HeJ, BALBc and C57BL6 mice. Changes in selected proteins, tumour perfusion and tumour necrotic fraction after CA4P treatment were then compared in individual animals. The cytokines KC and MCP-1 were observed to increase after CA4P treatment in all tested models. No correlation was found between KC or MCP-1 levels and tumour necrosis. However, tumour perfusion correlated (r = 0.89, p < 0.00001) with CA4P treatment efficacy as measured by necrotic fraction, suggesting that DCE-MRI may have utility in a clinical setting. (C) 2007 Elsevier Ltd. All rights reserved.