skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

Abstract

Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. Themore » reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.« less

Authors:
 [1];  [2];  [1]; ;  [2]; ;  [3]; ;  [1];  [1]
  1. Department of Radiotherapy and Radiation Oncology, Medical Faculty of Philipps University, Marburg (Germany)
  2. Department of Internal Medicine, Justus Liebig University, Giessen (Germany)
  3. Department of Radiology, Medical Faculty of Philipps University, Marburg (Germany)
Publication Date:
OSTI Identifier:
21436124
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 77; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2010.01.060; PII: S0360-3016(10)00262-2; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; BIOLOGICAL MARKERS; CARCINOMAS; LUNGS; NMR IMAGING; RADIOSENSITIVITY; BODY; DIAGNOSTIC TECHNIQUES; DISEASES; NEOPLASMS; ORGANS; RESPIRATORY SYSTEM; SENSITIVITY

Citation Formats

Fokas, Emmanouil, E-mail: emmanouil.fokas@yahoo.d, Haenze, Joerg, Kamlah, Florentine, Eul, Bastian G., Lang, Nico, Keil, Boris, Heverhagen, Johannes T., Engenhart-Cabillic, Rita, An Hanxiang, and Rose, Frank, E-mail: rosef@med.uni-marburg.d. Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model. United States: N. p., 2010. Web. doi:10.1016/j.ijrobp.2010.01.060.
Fokas, Emmanouil, E-mail: emmanouil.fokas@yahoo.d, Haenze, Joerg, Kamlah, Florentine, Eul, Bastian G., Lang, Nico, Keil, Boris, Heverhagen, Johannes T., Engenhart-Cabillic, Rita, An Hanxiang, & Rose, Frank, E-mail: rosef@med.uni-marburg.d. Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model. United States. doi:10.1016/j.ijrobp.2010.01.060.
Fokas, Emmanouil, E-mail: emmanouil.fokas@yahoo.d, Haenze, Joerg, Kamlah, Florentine, Eul, Bastian G., Lang, Nico, Keil, Boris, Heverhagen, Johannes T., Engenhart-Cabillic, Rita, An Hanxiang, and Rose, Frank, E-mail: rosef@med.uni-marburg.d. Sun . "Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model". United States. doi:10.1016/j.ijrobp.2010.01.060.
@article{osti_21436124,
title = {Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model},
author = {Fokas, Emmanouil, E-mail: emmanouil.fokas@yahoo.d and Haenze, Joerg and Kamlah, Florentine and Eul, Bastian G. and Lang, Nico and Keil, Boris and Heverhagen, Johannes T. and Engenhart-Cabillic, Rita and An Hanxiang and Rose, Frank, E-mail: rosef@med.uni-marburg.d},
abstractNote = {Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.},
doi = {10.1016/j.ijrobp.2010.01.060},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 77,
place = {United States},
year = {Sun Aug 01 00:00:00 EDT 2010},
month = {Sun Aug 01 00:00:00 EDT 2010}
}