Noninvasive Magnetic Resonance Imaging of Transport and Interstitial Fluid Pressure in Ectopic Human Lung Tumors
| Autor: | Raanan Margalit, Yaron Hassid, Hadassa Degani, Raya Eilam, Edna Furman-Haran |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Gadolinium DTPA
Cancer Research Lung Neoplasms Gadolinium Contrast Media Mice Nude chemistry.chemical_element Breast Neoplasms Mice In vivo Interstitial fluid Carcinoma Non-Small-Cell Lung Extracellular fluid Animals Humans Medicine Distribution (pharmacology) Lung cancer medicine.diagnostic_test business.industry Extracellular Fluid Magnetic resonance imaging medicine.disease Magnetic Resonance Imaging Oncology chemistry Drug delivery business Nuclear medicine |
| Zdroj: | Cancer Research. 66:4159-4166 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-05-3289 |
| Popis: | 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) |
| Databáze: | OpenAIRE |
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