Magnetic resonance imaging based analysis of tumor growth and vascular parameters in animal model of GBM following IV formulated of HET0016 treatments.

Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 a selective CYP450 inhibitor has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Tumor growth and vascular parameters (tumor blood volume, permeability and, extravascular and extracellular space volume) were determined by in vivo dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). The pharmacokinetics of HPßCD-HET0016 were evaluated in plasma and tumor tissues using IV and IP routes of administration. IV treatment with HPßCD-HET0016 decreased tumor growth, tumor blood volume, permeability and, extravascular and extracellular space volume, when compared with the vehicle group (