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.
abstract: 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.
authors.affiliation: Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Gunma, Japan. junsaito@sannet.ne.jp
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Saitoh
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Yoshizumi
authors.initials: Y
authors.lastname: Kitamoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Akimoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Norio
authors.initials: N
authors.lastname: Mitsuhashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: 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
chemical_list: D015415:Biomarkers; D009005:Monosaccharides; D009593:Nitroimidazoles; C468007:iodinated azomycin galactopyranoside; D010100:Oxygen