Intravascular contrast agent-enhanced MRI measuring contrast clearance and tumor blood volume and the effects of vascular modifiers in an experimental tumor.

Abstract

To examine the feasibility of using the MRI blood pool agent NC100150 for evaluation of tumor blood volume (TBV) estimates by both dynamic contrast-enhanced MRI (DCE-MRI) and susceptibility contrast MRI assays in an experimental tumor. Contrast agent clearance (K(trans); depends on perfusion and permeability) from the DCE-MRI time curves was estimated, and changes in TBV and K(trans) were measured after administration of two drugs that reduce perfusion by different mechanisms. The DCE-MRI experiments were simulated with expected physiologic values for the C3H mouse mammary carcinoma. The C3H tumor was examined by DCE-MRI and susceptibility contrast MRI with NC100150 (NC100150 Injection, Clariscan; Amersham Health, Oslo, Norway) after treatment with either hydralazine or combretastatin (Oxigene, Boston, MA). Simulations showed that reliable estimates of changes in TBV and K(trans) could be performed with DCE-MRI. Hydralazine was shown to reduce TBV as measured by both assays and to reduce K(trans). Dynamic contrast-enhanced MRI also suggested that TBV and K(trans) were reduced in combretastatin-treated tumors, and the TBV reduction was confirmed by susceptibility contrast MRI. Data suggested the drug to affect mainly the total TBV, whereas microvessels as such seemed less altered. The study supports the use of the combined DCE-MRI and susceptibility contrast MRI assay with a blood pool agent in characterizing tumors and their response to treatment.