(99m)Tc-tricarbonyl complexes functionalized with anthracenyl fragments: synthesis, characterization, and evaluation of their radiotoxic effects in murine melanoma cells

Cancer Biother Radiopharm. 2009 Oct;24(5):551-63. doi: 10.1089/cbr.2009.0647.

Abstract

Different pyrazolyl-diamine ligands bearing anthracenyl or anthrapyrazole functionalities as DNA-binding groups, at different positions of the chelator framework, were labeled with the fac-[(99m)Tc(CO)(3)](+) core. The resulting complexes, 1-4, are highly stable in vitro under physiologic conditions; all of them have been identified by high-performance liquid chromatography comparison with the Re congeners, with the exception of 3, that is anchored by an anthrapyrazole diamine ligand. Aiming to assess the ability of these complexes to target the cell nucleus and to induce enhanced cell death by effect of the Auger electrons emitted by (99m)Tc, the intracellular distribution and radiotoxicity of 1-4 were evaluated by using B16F1 murine melanoma cells. The radiotoxic effects depend very much on the position used to introduce the DNA-binding group and are well correlated with the nuclear uptake of the compounds. Complex 2, having the anthracenyl substituent at the 4-position of the pyrazolyl ring, rapidly entered the cells and accumulated inside the nucleus, exhibiting the highest radiotoxic effects. This compound induced an apoptotic cellular outcome, and its enhanced radiotoxic effects were certainly due to the Auger electrons emitted by the radiometal in close proximity to DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Anthracenes / therapeutic use*
  • Apoptosis
  • Cell Nucleus / radiation effects
  • Chelating Agents / chemical synthesis
  • Chelating Agents / therapeutic use
  • DNA / chemistry
  • Electrons
  • Ligands
  • Melanoma, Experimental
  • Mice
  • Models, Chemical
  • Protein Binding
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / therapeutic use*
  • Technetium / therapeutic use*

Substances

  • Anthracenes
  • Chelating Agents
  • Ligands
  • Radiopharmaceuticals
  • Technetium
  • DNA