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.
OBJECTIVE
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
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.
Saitoh
Jun-Ichi
J
Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Gunma, Japan. junsaito@sannet.ne.jp
Sakurai
Hideyuki
H
Suzuki
Yoshiyuki
Y
Muramatsu
Hiroyuki
H
Ishikawa
Hitoshi
H
Kitamoto
Yoshizumi
Y
Akimoto
Tetsuo
T
Hasegawa
Masatoshi
M
Mitsuhashi
Norio
N
Nakano
Takashi
T
D000818:Animals; D015415:Biomarkers; D015687:Cell Hypoxia; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D009005:Monosaccharides / Q000493:pharmacokinetics; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D009929:Organ Size; D010100:Oxygen / Q000032:analysis*; D010313:Partial Pressure; D011836:Radiation Tolerance
D015415:Biomarkers; D009005:Monosaccharides; D009593:Nitroimidazoles; C468007:iodinated azomycin galactopyranoside; D010100:Oxygen