Preparation and biological evaluation of ⁹⁹mTc-N4IPA for single photon emission computerized tomography imaging of hypoxia in mouse tumor

Eur J Med Chem. 2013 Nov:69:223-31. doi: 10.1016/j.ejmech.2013.08.005. Epub 2013 Aug 24.

Abstract

In order to develop technetium-99m labeled nitroimidazole imaging agent for hypoxia in tumor, we have synthesized (99m)Tc-1-(4-nitroimidazole-yl)-propanhydroxyiminoamide, (99m)Tc-N4IPA complex, in high radiochemical purity and radiochemical yield. The biological evaluation of this complex includes the in vitro/vivo stability, cell uptake and Single Photon Emission Computerized Tomography (SPECT) imaging in mouse tumor models, respectively. These results demonstrate that (99m)Tc-N4IPA may have potential as clinical hypoxia imaging agent. The key features of the biological evaluation include the following: (1) the autoradiogram of (99m)Tc-N4IPA complex in tissue samples of hypoxia overlaps with the area stained by hypoxyprobe-1; (2) SPECT imaging of U87-bearing mice clearly identifies tumors 4 h post injection of (99m)Tc-N4IPA, reaching ID% of 8.48 ± 4.51; (3) the main pathways of excretion of (99m)Tc-N4IPA are through kidneys and livers in both A549 or U87-bearing tumor mice.

Keywords: 4-Nitroimidazoles; Hypoxia imaging; Technium-99m; Tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Humans
  • Hypoxia / diagnosis*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / diagnosis*
  • Organotechnetium Compounds* / administration & dosage
  • Organotechnetium Compounds* / chemistry
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon*

Substances

  • Organotechnetium Compounds
  • technetium 99m 1-(4-nitroimidazolyl)propanehydroxyiminoamide