This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hassid, Y. Articles by Degani, H. Search for Related Content PubMed PubMed Citation Articles by Hassid, Y. Articles by Degani, H.

Noninvasive Magnetic Resonance Imaging of Transport and Interstitial Fluid Pressure in Ectopic Human Lung Tumors

Departments of ¹ Biological Regulation and ² Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel

Requests for reprints: Hadassa Degani, Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel 76100. Phone: 972-8-9342017; Fax 972-8-936154; E-mail: hadassa.degnani{at}weizmann.ac.il.

Tumor response to blood borne drugs is critically dependent on the efficiency of vascular delivery and transcapillary transfer. However, increased tumor interstitial fluid pressure (IFP) forms a barrier to transcapillary transfer, leading to resistance to drug delivery. We present here a new, noninvasive method which estimates IFP and its spatial distribution in vivo using contrast-enhanced magnetic resonance imaging (MRI). This method was tested in ectopic human non–small-cell lung cancer which exhibited a high IFP of 28 mm Hg and, for comparison, in orthotopic MCF7 human breast tumors which exhibited a lower IFP of 14 mm Hg, both implanted in nude mice. The MRI protocol consisted of slow infusion of the contrast agent [gadolinium-diethylenetriaminepentaacetic acid (GdDTPA)] into the blood for 2 hours, sequential acquisition of images before and during the infusion, and measurements of T₁ relaxation rates before infusion and after blood and tumor GdDTPA concentration reached a steady state. Image analysis yielded parametric images of steady-state tissue GdDTPA concentration with high values of this concentration outside the tumor boundaries, 1 mmol/L, declining in the tumor periphery to 0.5 mmol/L, and then steeply decreasing to low or null values. The distribution of steady-state tissue GdDTPA concentration reflected the distribution of IFP, showing an increase from the rim inward, with a high IFP plateau inside the tumor. The changes outside the borders of the tumors with high IFP were indicative of convective transport through the interstitium. This work presents a noninvasive method for assessing the spatial distribution of tumor IFP and mapping barriers to drug delivery and transport. (Cancer Res 2006; 66(8): 4159-66)