Tc-99m-Tricarbonyl Complexes Functionalized with Anthracenyl Fragments: Synthesis, Characterization, and Evaluation of Their Radiotoxic Effects in Murine Melanoma Cells

RF Vitor, T Esteves, F Marques, P Raposinho, A Paulo, A.S. Rodrigues, J. Rueff, S Casimiro, L Costa, I. Santos

Research output: Contribution to journalArticle

18 Citations (Scopus)

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-[Tc-99m(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 99mTc, 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.
Original languageEnglish
Pages (from-to)551-563
Number of pages13
JournalCancer biotherapy & radiopharmaceuticals
Volume24
Issue number5
DOIs
Publication statusPublished - 1 Oct 2009

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Melanoma
Diamines
DNA
Electrons
Ligands
Carbon Monoxide
Chelating Agents
Cell Nucleus
Cell Death
High Pressure Liquid Chromatography
anthrapyrazole
In Vitro Techniques

Keywords

  • technetium-99m
  • anthracene derivatives
  • Auger electrons
  • nuclear targeting
  • radiotoxicity

Cite this

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title = "Tc-99m-Tricarbonyl Complexes Functionalized with Anthracenyl Fragments: Synthesis, Characterization, and Evaluation of Their Radiotoxic Effects in Murine Melanoma Cells",
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-[Tc-99m(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 99mTc, 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.",
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Tc-99m-Tricarbonyl Complexes Functionalized with Anthracenyl Fragments: Synthesis, Characterization, and Evaluation of Their Radiotoxic Effects in Murine Melanoma Cells. / Vitor, RF; Esteves, T; Marques, F; Raposinho, P; Paulo, A; Rodrigues, A.S.; Rueff, J.; Casimiro, S; Costa, L; Santos, I.

In: Cancer biotherapy & radiopharmaceuticals, Vol. 24, No. 5, 01.10.2009, p. 551-563.

Research output: Contribution to journalArticle

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