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.
Salmon
Beth A
BA
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.
Salmon
Howard W
HW
Siemann
Dietmar W
DW
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D003287:Contrast Media; D005682:Gadolinium; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D012509:Sarcoma / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy*; D013267:Stilbenes / Q000627:therapeutic use*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D013267:Stilbenes; D005682:Gadolinium; C058728:fosbretabulin