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.

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.

• Authors: Jun-Ichi Saitoh, Hideyuki Sakurai, Yoshiyuki Suzuki, Hiroyuki Muramatsu, Hitoshi Ishikawa, Yoshizumi Kitamoto, Tetsuo Akimoto, Masatoshi Hasegawa, Norio Mitsuhashi, Takashi Nakano
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 54 Issue 3 Pg. 903-9 (Nov 01 2002) ISSN: 0360-3016 [Print] United States
• PMID: 12377344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Monosaccharides
• Nitroimidazoles
• iodinated azomycin galactopyranoside
• Oxygen

Topics

• Animals
• Biomarkers
• Cell Hypoxia
• Female
• Magnetic Resonance Spectroscopy
• Male
• Mammary Neoplasms, Animal (metabolism, pathology, radiotherapy)
• Mice
• Mice, Inbred C3H
• Monosaccharides (pharmacokinetics)
• Nitroimidazoles (pharmacokinetics)
• Organ Size
• Oxygen (analysis)
• Partial Pressure
• Radiation Tolerance