RRC ID 41695
Author Saitoh J, Sakurai H, Suzuki Y, Muramatsu H, Ishikawa H, Kitamoto Y, Akimoto T, Hasegawa M, Mitsuhashi N, Nakano T.
Title Correlations between in vivo tumor weight, oxygen pressure, 31P NMR spectroscopy, hypoxic microenvironment marking by beta-D-iodinated azomycin galactopyranoside (beta-D-IAZGP), and radiation sensitivity.
Journal Int. J. Radiat. Oncol. Biol. Phys.
Abstract PURPOSE:The purpose of this study is to evaluate the amount of hypoxic fraction in a rodent tumor by means of polarographic oxygen electrode, phosphorus-31 magnetic resonance spectroscopy (31P-MRS), and a newly synthesized hypoxic marker, beta-D-iodinated azomycin galactopyranoside (beta-D-IAZGP). We also investigated the radiosensitivity for tumors of different weights.
METHODS AND MATERIALS:Murine mammary carcinoma cells, FM3A, were subcutaneously implanted into the back of 5-week-old male C3H/He mice. beta-D-IAZGP radiolabeled with 123I or with 125I was injected intravenously into tumor-bearing mice, and marker distribution was measured by nuclear medicine procedures. Radiosensitivity of the tumor was measured by the in vivo/in vitro clonogenic assay. Tumor oxygenation status was also measured directly by polarographic oxygen electrodes and indirectly estimated from 31P-MR spectra.
RESULTS:Higher accumulation of 123I-beta-D-IAZGP was observed in the tumors than in normal tissues at 24 h after administration. As to biodistribution of 125I-beta-D-IAZGP, the tumor/blood ratio varied widely, but correlated significantly with tumor weight. Mean oxygen pressure (pO2) values and ratios of nucleoside triphosphate beta to inorganic phosphate (beta-ATP/Pi) and of phosphocreatine to inorganic phosphate (PCr/Pi) decreased significantly with the increase in tumor volume. As tumor volume increased, the surviving fraction of cells from tumors irradiated in vivo increased significantly.
CONCLUSIONS:The increase in tumor volume was significantly correlated with a reduction in mean pO2, a decrease in the ratios of beta-ATP/Pi or PCr/Pi, an increase in uptake of beta-D-IAZGP, and an increase in radioresistance. Because the uptake of beta-D-IAZGP can be measured noninvasively by nuclear medicine techniques, it could be clinically useful for monitoring hypoxia in human tumors.
Volume 54(3)
Pages 903-9
Published 2002-11-1
DOI 10.1016/s0360-3016(02)03013-4
PII S0360301602030134
PMID 12377344
MeSH Animals Biomarkers Cell Hypoxia* Female Magnetic Resonance Spectroscopy Male Mammary Neoplasms, Animal / metabolism* Mammary Neoplasms, Animal / pathology* Mammary Neoplasms, Animal / radiotherapy Mice Mice, Inbred C3H Monosaccharides / pharmacokinetics Nitroimidazoles / pharmacokinetics Organ Size Oxygen / analysis* Partial Pressure Radiation Tolerance*
IF 5.554
Times Cited 17
Human and Animal Cells