Imaging acute effects of bevacizumab on tumor vascular kinetics in a preclinical orthotopic model of U251 glioma.

摘要: The effect of a human vascular endothelial growth factor antibody on the vasculature tumor grown in rat brain was studied. Using dynamic contrast-enhanced magnetic resonance imaging, effects intravenous bevacizumab (Avastin; 10 mg/kg) were examined before and at postadministration times 1, 2, 4, 8, 12 24 h (N = 26; 4-5 per time point) model orthotopic, U251 glioblastoma (GBM). commonly estimated parameters for an MR contrast agent were: (i) plasma distribution volume (vp ), (ii) forward volumetric transfer constant (Ktrans ) (iii) reverse (kep ). In addition, extracellular (VD (VD-tumor edge (VD-edge mostly normal periphery (VD-peri along with blood flow (TBF), peri-tumoral hydraulic conductivity (K) interstitial (Flux) fluid pressure (TIFP). Studied as % changes from baseline, 2-h post-treatment point began showing significant decreases vp , VD-tumor, VD-edge VD-peri well K, these persisting 4 8 h -edge -peri (t-tests; p < 0.05-0.01). Decreases Ktrans observed 2- 4-h points (p 0.05), while fraction (ve ; = /kep showed decrease only 0.05). Sustained Flux 2 to 0.01) TBF TIFP delayed responses, increases former latter 12 h. These imaging biomarkers kinetics describe short-term temporal physical spaces flows GBM after Avastin administration.