Measurement of the extracellular volume of human melanoma xenografts by contrast enhanced magnetic resonance imaging

The magnitude of the extracellular volume fraction (ECV) of tumors is of im portance for the transport of macromolecular therapeutic agents from the ve ssel wall to the tumor cells. The aim of this study was to develop a method for measurement of tumor ECV by contrast enhanced MRI. Tumors of two human amelanotic melanoma xenograft lines (A-07 and R-18) grown intradermally in Balb/c nu/nu mice were used as model system, and muscle tissue was used as control. The renal arteries of the mice were ligated prior to i.v. adminis tration of Gd-DTPA, and an MRI protocol for calculating Gd-DTPA concentrati on in tissue was followed. ECV was calculated from the Gd-DTPA concentratio ns in the tissue and in a plasma sample. In muscle tissue, the concentratio n reached a constant level after 1 min and the ECV was calculated to be 0.1 2 (+/- 0.01), consistent with values reported in the literature. Individual tumors showed large differences in the uptake of Gd-DTPA. The Cd-DTPA conc entration in the tissue at 40 min after the Gd-DTPA administration was used to calculate tumor ECV. The ECV was found to differ significantly among re gions of individual tumors and among individual tumors. The ECV ranged from 0.075 to 0.33 for A-07 tumors and from 0.016 to 0.097 for R-18 tumors. The intra- and intertumor heterogeneity in ECV was confirmed by histologic fin dings, showing that contrast enhanced MRI is suitable for non-invasive stud ies of the ECV in experimental tumors without necrosis. (C) 2000 Elsevier S cience Inc. All rights reserved.