Purpose: The goal of the present study was to examine the safety and efficacy of the vascular disrupting agent (VDA) EPC2407 (Crolibulin™) in experimental glioma models using bioluminescence imaging (BLI) and magnetic resonance imaging (MRI).
Procedures: Experimental imaging studies were performed in subcutaneous human U87 glioma xenografts and orthotopic murine gliomas established by intracranial implantation of luciferase-transfected glioma cells (GL261-luc). Correlative histopathology and long-term survival analysis was also performed.
Results: Treatment with EPC2407 decreased tumor perfusion and increased necrosis and tumor doubling times in subcutaneous U87 xenografts. Dynamic BLI and T1-weighted contrast-enhanced MRI showed reduction in blood flow of intracranial GL261-luc gliomas within a few hours of VDA treatment. T2-weighted MRI did not show any evidence of hemorrhaging or edema in uninvolved brain tissue of EPC2407-treated animals. A significant increase in median survival (p < 0.05) was observed in the orthotopic GL261-luc model following VDA treatment compared to untreated controls.
Conclusions: We demonstrate, for the first time, the biological activity of EPC2407 in experimental gliomas. Further investigation into the potential of VDAs in combination with chemoradiation therapy against gliomas is warranted.
Keywords: Bioluminescence imaging; Blood brain barrier; Glioblastoma; Magnetic resonance imaging; Vascular disrupting agents.