Correlations between in vivo tumor weight, oxygen pressure, 31P NMR spectroscopy, hypoxic microenvironment marking by β-D-iodinated azomycin galactopyranoside (β-D-IAZGP), and radiation sensitivity

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, β-D-iodinated azomycin galactopyranoside (β-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. β-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-β-D-IAZGP was observed in the tumors than in normal tissues at 24 h after administration. As to biodistribution of 125I-β-D-IAZGP, the tumor/blood ratio varied widely, but correlated significantly with tumor weight. Mean oxygen pressure (pO 2) values and ratios of nucleoside triphosphate β to inorganic phosphate (β-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 pO 2, a decrease in the ratios of β-ATP/Pi or PCr/Pi, an increase in uptake of β-D-IAZGP, and an increase in radioresistance. Because the uptake of β-D-IAZGP can be measured noninvasively by nuclear medicine techniques, it could be clinically useful for monitoring hypoxia in human tumors.