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

Purpose: 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 Iran,; 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. Methods and Materials: The DCE-MRI experiments were simulated with expected physiologic values for the C3H mouse mammary carcinoma. The C3H tumor was examined by DCE-MR1 and susceptibility contrast MRI with NC100150 (NC100150 Injection, Clariscan; Amersham Health, Oslo, Norway) after treatment with either hydralazine or combretastatin (Oxigene, Boston, MA). Results: 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. Conclusion: The study supports the use of the combined DCE-MR1 and susceptibility contrast MRI assay with a blood pool agent in characterizing tumors and their response to treatment. (c) 2005 Elsevier Inc.