crolibulin and Glioma

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).. 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.. 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.. 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.

Topics: Animals; Antineoplastic Agents; Benzopyrans; Blood Vessels; Blood-Brain Barrier; Brain Neoplasms; Cell Line, Tumor; Contrast Media; Glioma; Humans; Luminescent Measurements; Magnetic Resonance Imaging; Mice, Inbred C57BL; Mice, Nude; Treatment Outcome; Xenograft Model Antitumor Assays