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Title: Dynamic Contrast-Enhanced Magnetic Resonance Imaging of the Metastatic Potential of Melanoma Xenografts

Abstract

Purpose: Gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been suggested as a useful noninvasive method for characterizing the physiologic microenvironment of tumors. In the present study, we investigated whether Gd-DTPA-based DCE-MRI has the potential to provide biomarkers for hypoxia-associated metastatic dissemination. Methods and Materials: C-10 and D-12 melanoma xenografts were used as experimental tumor models. Pimonidazole was used as a hypoxia marker. A total of 60 tumors were imaged, and parametric images of K{sup trans} (volume transfer constant of Gd-DTPA) and v{sub e} (fractional distribution volume of Gd-DTPA) were produced by pharmacokinetic analysis of the DCE-MRI series. The host mice were killed immediately after DCE-MRI, and the primary tumor and the lungs were resected and prepared for histologic assessment of the fraction of pimonidazole-positive hypoxic tissue and the presence of lung metastases, respectively. Results: Metastases were found in 11 of 26 mice with C-10 tumors and 14 of 34 mice with D-12 tumors. The primary tumors of the metastatic-positive mice had a greater fraction of hypoxic tissue (p = 0.00031, C-10; p < 0.00001, D-12), a lower median K{sup trans} (p = 0.0011, C-10; p < 0.00001, D-12), and a lower median v{sub e} (pmore » = 0.014, C-10; p = 0.016, D-12) than the primary tumors of the metastatic-negative mice. Conclusions: These findings support the clinical attempts to establish DCE-MRI as a method for providing biomarkers for tumor aggressiveness and suggests that primary tumors characterized by low K{sup trans} and low v{sub e} values could have a high probability of hypoxia-associated metastatic spread.« less

Authors:
; ;  [1];  [1]
  1. Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo (Norway)
Publication Date:
OSTI Identifier:
22056350
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 83; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ACETIC ACID; ANOXIA; BIOLOGICAL MARKERS; GADOLINIUM COMPOUNDS; IMAGES; LUNGS; MELANOMAS; METASTASES; NMR IMAGING; PROBABILITY

Citation Formats

Ovrebo, Kirsti Marie, Ellingsen, Christine, Galappathi, Kanthi, and Rofstad, Einar K., E-mail: einar.k.rofstad@rr-research.no. Dynamic Contrast-Enhanced Magnetic Resonance Imaging of the Metastatic Potential of Melanoma Xenografts. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2011.12.019.
Ovrebo, Kirsti Marie, Ellingsen, Christine, Galappathi, Kanthi, & Rofstad, Einar K., E-mail: einar.k.rofstad@rr-research.no. Dynamic Contrast-Enhanced Magnetic Resonance Imaging of the Metastatic Potential of Melanoma Xenografts. United States. doi:10.1016/J.IJROBP.2011.12.019.
Ovrebo, Kirsti Marie, Ellingsen, Christine, Galappathi, Kanthi, and Rofstad, Einar K., E-mail: einar.k.rofstad@rr-research.no. Tue . "Dynamic Contrast-Enhanced Magnetic Resonance Imaging of the Metastatic Potential of Melanoma Xenografts". United States. doi:10.1016/J.IJROBP.2011.12.019.
@article{osti_22056350,
title = {Dynamic Contrast-Enhanced Magnetic Resonance Imaging of the Metastatic Potential of Melanoma Xenografts},
author = {Ovrebo, Kirsti Marie and Ellingsen, Christine and Galappathi, Kanthi and Rofstad, Einar K., E-mail: einar.k.rofstad@rr-research.no},
abstractNote = {Purpose: Gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been suggested as a useful noninvasive method for characterizing the physiologic microenvironment of tumors. In the present study, we investigated whether Gd-DTPA-based DCE-MRI has the potential to provide biomarkers for hypoxia-associated metastatic dissemination. Methods and Materials: C-10 and D-12 melanoma xenografts were used as experimental tumor models. Pimonidazole was used as a hypoxia marker. A total of 60 tumors were imaged, and parametric images of K{sup trans} (volume transfer constant of Gd-DTPA) and v{sub e} (fractional distribution volume of Gd-DTPA) were produced by pharmacokinetic analysis of the DCE-MRI series. The host mice were killed immediately after DCE-MRI, and the primary tumor and the lungs were resected and prepared for histologic assessment of the fraction of pimonidazole-positive hypoxic tissue and the presence of lung metastases, respectively. Results: Metastases were found in 11 of 26 mice with C-10 tumors and 14 of 34 mice with D-12 tumors. The primary tumors of the metastatic-positive mice had a greater fraction of hypoxic tissue (p = 0.00031, C-10; p < 0.00001, D-12), a lower median K{sup trans} (p = 0.0011, C-10; p < 0.00001, D-12), and a lower median v{sub e} (p = 0.014, C-10; p = 0.016, D-12) than the primary tumors of the metastatic-negative mice. Conclusions: These findings support the clinical attempts to establish DCE-MRI as a method for providing biomarkers for tumor aggressiveness and suggests that primary tumors characterized by low K{sup trans} and low v{sub e} values could have a high probability of hypoxia-associated metastatic spread.},
doi = {10.1016/J.IJROBP.2011.12.019},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 1,
volume = 83,
place = {United States},
year = {2012},
month = {5}
}