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Title: Thymidine analogues to assess microperfusion in human tumors

Abstract

Purpose: To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Methods and Materials: Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. Results: We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r 85, p = 0.0004), despite some mismatches on a per-vessel basis. Conclusions: Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation.

Authors:
 [1];  [2];  [2];  [1];  [2];  [2];  [3];  [4]
  1. Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands)
  2. Department of Radiation Oncology, University Medical Center Nijmegen, Nijmegen (Netherlands)
  3. Department of Radiation Oncology, University Hospital Gasthuisberg, Leuven (Belgium)
  4. Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands). E-mail: a.begg@nki.nl
Publication Date:
OSTI Identifier:
20698628
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 62; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2005.03.063; PII: S0360-3016(05)00601-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; BIOPSY; BLOOD VESSELS; GLIOMAS; HEAD; IODODEOXYURIDINE; LABELLING; NECK; THYMIDINE

Citation Formats

Janssen, Hilde L., Ljungkvist, Anna S., Rijken, Paul F., Sprong, Debbie, Bussink, Jan, Kogel, Albert J. van der, Haustermans, Karin M., and Begg, Adrian C. Thymidine analogues to assess microperfusion in human tumors. United States: N. p., 2005. Web. doi:10.1016/j.ijrobp.2005.03.063.
Janssen, Hilde L., Ljungkvist, Anna S., Rijken, Paul F., Sprong, Debbie, Bussink, Jan, Kogel, Albert J. van der, Haustermans, Karin M., & Begg, Adrian C. Thymidine analogues to assess microperfusion in human tumors. United States. doi:10.1016/j.ijrobp.2005.03.063.
Janssen, Hilde L., Ljungkvist, Anna S., Rijken, Paul F., Sprong, Debbie, Bussink, Jan, Kogel, Albert J. van der, Haustermans, Karin M., and Begg, Adrian C. 2005. "Thymidine analogues to assess microperfusion in human tumors". United States. doi:10.1016/j.ijrobp.2005.03.063.
@article{osti_20698628,
title = {Thymidine analogues to assess microperfusion in human tumors},
author = {Janssen, Hilde L. and Ljungkvist, Anna S. and Rijken, Paul F. and Sprong, Debbie and Bussink, Jan and Kogel, Albert J. van der and Haustermans, Karin M. and Begg, Adrian C.},
abstractNote = {Purpose: To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Methods and Materials: Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. Results: We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r 85, p = 0.0004), despite some mismatches on a per-vessel basis. Conclusions: Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation.},
doi = {10.1016/j.ijrobp.2005.03.063},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 62,
place = {United States},
year = 2005,
month = 7
}