Preparation and biodistribution of technetium-99m-labeled 1-(2-nitroimidazole-1-yl)-propanhydroxyiminoamide (N2IPA) as a tumor hypoxia marker

Nucl Med Biol. 2004 Feb;31(2):199-203. doi: 10.1016/j.nucmedbio.2003.08.007.

Abstract

A new hydroxyiminoamide ligand, 1-(2-nitroimidazole-1-yl)-propanhydroxyiminoamide (N2IPA) was synthesized. The biodistribution of (99m)Tc-N2IPA in mice bearing S180 tumor demonstrated that the complex showed a selective accumulation in tumor and slow clearance from it. The tumor-to-tissue uptake ratios increased with time. At 4 hours after injection, the uptake ratios of tumor to muscle, blood, liver, heart, and lung reached 8.4, 1.5, 0.6, 2.9, and 2.3, respectively. Moreover, the tumor-to-liver uptake ratio steadily increased to 0.9 at 8 hours and 2.3 at 24 hours. The complex showed little uptake and quick clearance in blood, lung and other organs. Compared with other proposed hypoxia-imaging agents, this novel agent has advantages of higher tumor-to-muscle and tumor-to-blood uptake ratios and easier synthesis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Cell Hypoxia*
  • Cell Line, Tumor
  • Imidazoles / chemistry
  • Imidazoles / pharmacokinetics*
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Mice
  • Organ Specificity
  • Organotechnetium Compounds / chemistry
  • Organotechnetium Compounds / pharmacokinetics*
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Sarcoma / diagnostic imaging*
  • Sarcoma / metabolism*
  • Tissue Distribution

Substances

  • Biomarkers, Tumor
  • Imidazoles
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • technetium-99m-1-(2-nitroimidazole-1-yl)-propanhydroxyiminoamide