Cilengitide-Induced Temporal Variations in Transvascular Transfer Parameters of Tumor Vasculature in a Rat Glioma Model: Identifying Potential MRI Biomarkers of Acute Effects

摘要: Increased efficacy of radiotherapy (RT) 4-8 h after Cilengitide treatment has been reported. We hypothesized that the effects on tumor transvascular transfer parameters might underlie, and thus predict, this potentiation. Athymic rats with orthotopic U251 glioma were studied at ~21 days implantation using dynamic contrast-enhanced (DCE)-MRI. Vascular parameters, viz: plasma volume fraction (vp), forward constant (Ktrans) interstitial (ve) a contrast agent, determined in vasculature once before, again cohorts 2, 4, 8, 12 24 administration (4 mg/kg; N = 31; 6-7 per cohort). Perfusion-fixed brain sections stained for von Willebrand factor to visualize vascular segments. A comparison pre- post-treatment showed differences between MR indices before pivoted around 8 time point, 2 4 groups showing increases, decreases, values point close baseline. The parameter group significant Ktrans (p 0.0001 ve 0,0271). staining little variation Cilengitide. normalization occurring coincided similar previous reports increased when RT followed by h. Pharmacological potential increase sensitivity RT. Evaluating acute temporal responses putative anti-angiogenic drugs may help optimizing their combination other modalities.