Quantitative assessment of uptake and distribution of iron oxide particles (NC100150) in human melanoma xenografts by contrast-enhanced MRI

The intratumor heterogeneity in uptake of iron oxide particles (NC100150) in human melanoma xenografts was studied by MRI and the uptake was related to the blood volume fraction, BV, and the permeability surface area product, PS, in an attempt to identify transport barriers limiting the delivery of large macromolecular therapeutic agents to tumors. Dynamic MRI was performed by using spoiled gradient recalled sequences and the extravascular uptake of NC100150, BV, and PS were calculated for each tumor voxel by using a two-compartment tissue model. The uptake of NC100150 and BV were low in the tumor center and increased gradually towards the tumor periphery, whereas there was no radial gradient in PS. Significant correlations were found between the voxel values of the parameters. Thus, PS was inversely correlated to BV, and this correlation was stronger in the center than in the periphery of the tumors. The uptake of NC100150 was positively correlated to PS and this correlation was strong in the tumor periphery, where the blood perfusion is high, and weak in the tumor center, where the blood perfusion is low. In contrast, the uptake of NC100150 was not correlated to BV in any tumor region. These observations suggest that the extravascular uptake of NC100150 was limited primarily by the microvascular permeability in the tumor periphery and primarily by the blood perfusion in the tumor center. (C) 2004 Wiley-Liss, Inc.