Induction of DNA-Double-Strand Breaks by Auger Electrons from 99mTc Complexes with DNA-Binding Ligands
✍ Scribed by Pascal Häfliger; Nikos Agorastos; Bernhard Spingler; Oleg Georgiev; Giampietro Viola; Roger Alberto
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 217 KB
- Volume
- 6
- Category
- Article
- ISSN
- 1439-4227
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✦ Synopsis
Abstract
The potential of certain Auger electron emitting nuclides for systemic radiotherapeutic applications has recently gained much attention. In particular, the ability of several nuclides, including ^111^In, ^125^I, and ^123^I, to induce DNA double‐strand breaks (dsb), a good indicator of cytotoxicity, has been extensively studied. However, this ability has never previously been shown experimentally for ^99m^Tc, which, besides the well‐known γ radiation that is used for diagnostic applications, also emits an average of 1.1 conversion electrons and 4 Auger or Coster–Kronig electrons per decay. Owing to the short range of Auger electrons, the radionuclide needs to be located very close to the DNA for dsb to occur. We synthesized two cationic ^99m^Tc^I^–tricarbonyl complexes with pendant DNA binders, pyrene and anthraquinone. The X‐ray crystal structures of the two complexes could be elucidated. Linear dichroism and UV/Vis spectroscopy revealed that the complex with pyrene intercalates DNA with a stability constant, K, of 1.1×10^6^ M^−1^, while the analogous complex with anthraquinone interacts with DNA in a groove‐binding mode and has an affinity value of K=8.9×10^4^ M^−1^. We showed with ϕX174 double‐stranded DNA that the corresponding ^99m^Tc complexes induce a significant amount of dsb, whereas non‐DNA‐binding [TcO~4~]^−^ and nonradioactive Re compounds did not. These results indicate that the Auger electron emitter ^99m^Tc can induce dsb in DNA when decaying in its direct vicinity and this implies potential for systemic radiotherapy with ^99m^Tc complexes.