Publication Date:
2012-04-16
Description:
Vascular-targeted therapies have shown promise as adjuvant cancer treatment. As these agents undergo clinical evaluation, sensitive imaging biomarkers are needed to assess drug target interaction and treatment response. In this study, dynamic contrast enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI) were evaluated for detecting response of intracerebral 9 L gliosarcomas to the antivascular agent VEGF-Trap, a fusion protein designed to bind all forms of Vascular Endothelial Growth Factor-A (VEGF-A) and Placental Growth Factor (PGF). Rats with 9 L tumors were treated twice weekly for two weeks with vehicle or VEGF-Trap. DCE- and DW-MRI were performed one day prior to treatment initiation and one day following each administered dose. Kinetic parameters ( K trans , volume transfer constant; k ep , efflux rate constant from extravascular/extracellular space to plasma; and v p , blood plasma volume fraction) and the apparent diffusion coefficient (ADC) over the tumor volumes were compared between groups. A significant decrease in kinetic parameters was observed 24 hours following the first dose of VEGF-Trap in treated versus control animals ( p 〈 0.05) and was accompanied by a decline in ADC values. In addition to the significant hemodynamic effect, VEGF-Trap treated animals exhibited significantly longer tumor doubling times ( p 〈 0.05) compared to the controls. Histological findings were found to support imaging response metrics. In conclusion, kinetic MRI parameters and change in ADC have been found to serve as sensitive and early biomarkers of VEGF-Trap anti-vascular targeted therapy. Copyright © 2011 John Wiley & Sons, Ltd. DCE-MRI and MRI DW-MRI were evaluated for detecting response of intracerebral 9L gliomas to the antivascular agent VEGF-Trap. A significant drop in permeability parameters was observed 24 hours following the first dose of VEGF-Trap accompanied by a decline in ADC values. VEGF-Trap-treated animals also required a significantly longer time for their tumors to reach 300% initial tumor volume compared to the untreated animals.
Print ISSN:
0952-3480
Electronic ISSN:
1099-1492
Topics:
Medicine