Synthesis, radiolabeling and biological evaluation of propylene amine oxime complexes containing nitrotriazoles as hypoxia markers

Molecules. 2012 Jun 4;17(6):6808-20. doi: 10.3390/molecules17066808.

Abstract

Two propylene amine oxime (PnAO) complexes, 1, containing a 3-nitro-1,2,4-triazole and 2, containing two 3-nitro-1,2,4-triazoles, were synthesized and radiolabeled with (99m)Tc in high labeling yields. Cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were tested using a S180 cells line. Under anoxic conditions, the cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were 33.7 ± 0.2% and 35.0 ± 0.7% at 4 h, whereas the normoxic uptakes of the two complexes were 6.0 ± 1.6% and 4.6 ± 0.9%, respectively. Both (99m)Tc-1 and (99m)Tc-2 displayed significant anoxic/normoxic differentials. The cellular uptakes were highly dependent on oxygen and temperature. Biodistribution studies revealed that both (99m)Tc-1 and (99m)Tc-2 showed a selective localization in tumor and slow clearance from it. At 4 h, the tumor-to-muscle ratios (T/M) were 3.79 for (99m)Tc-1 and 4.58 for (99m)Tc-2. These results suggested that (99m)Tc-labeled PnAO complexes (99m)Tc-1 and (99m)Tc-2 might serve as novel hypoxia markers. By introducing a second nitrotriazole redox center, the hypoxic accumulation of the marker was slightly enhanced.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / chemistry
  • Biomarkers / metabolism
  • Cell Hypoxia
  • Cell Line, Tumor
  • Isotope Labeling
  • Male
  • Mice
  • Organotechnetium Compounds / chemical synthesis*
  • Organotechnetium Compounds / chemistry
  • Organotechnetium Compounds / metabolism*
  • Quality Control
  • Technetium Tc 99m Exametazime / analogs & derivatives*
  • Technetium Tc 99m Exametazime / chemical synthesis*
  • Technetium Tc 99m Exametazime / chemistry
  • Technetium Tc 99m Exametazime / metabolism*
  • Temperature
  • Tissue Distribution
  • Triazoles / chemistry

Substances

  • Biomarkers
  • Organotechnetium Compounds
  • Triazoles
  • Technetium Tc 99m Exametazime