In vivo prediction of vascular susceptibility to vascular endothelial growth factor withdrawal: Magnetic resonance imaging of C6 rat glioma in nude mice

One of the hallmarks of tumor neovasculature is the prevalence of immature vessels manifested by the low degree of recruitment of vascular mural cells such as pericytes and smooth muscle cells. This difference in the architec ture of the vascular bed provides an important therapeutic window for infli cting tumor-selective vascular damage. Here we demonstrate the application of gradient echo magnetic resonance imaging (MRI) for noninvasive in vivo m apping of vascular maturation, manifested by the ability of mature vessels to dilate in response to elevated levels of CO2. Histological alpha-actin s taining showed a match between dilating vessels detected by MRI and vessels coated with smooth muscle cells. Switchable, vascular endothelial growth f actor (VEGF)-overexpressing tumors (C6-pTET-VEGF rat glioma s.c, tumors in nude mice) displayed high vascular function and significant vascular damage upon VEGF withdrawal. However, damage was restricted to nondilating vessel s, whereas mature dilating tumor vessels were resistant to VEGF withdrawal. Thus, MRI provides in vivo visualization of vascular maturity and prognosi s of vascular obliteration induced by VEGF withdrawal.