Detection of Auger Electron Induced Strand Breaks on Plasmid DNA Caused by Technetium-99m Labeled Pyrene Derivatives


Detection of Auger Electron Induced Strand Breaks on Plasmid DNA Caused by Technetium-99m Labeled Pyrene Derivatives

Wunderlich, G.; Reissig, F.; Mamat, C.; Pietzsch, H.-J.; Kotzerke, J.; Steinbach, J.

Simultaneously with the known γ-emission, 99mTc causes radical-mediated DNA damage due to Auger electrons, which were also emitted. We have synthesized a series of new 99mTc-labeled pyrene derivatives (common DNA intercalators) with varied distances between the pyrene moiety and the radionuclide (Fig. 1). Plasmids (pUC 19) enable the investigation of the unprotected interactions between the labeled pyrene derivatives (3-15MBq) and DNA that results in single-strand breaks (SSB) or double-strand breaks (DSB) separated by gel electrophoresis in 1.4% agarose gel and quantified by fluorescent staining. We used the 99mTc(CO)3-core for pyrene labeling. 99mTc was tightly bound to the plasmid DNA and its damage is mainly dependent on the chain length between the pyrene residue and the Tc-core. It could not be completely prevented by DMSO, a known free radical scavenger. The effectiveness of the DNA-binding 99mTc-labeled pyrene derivatives was demonstrated by comparison to non-DNA-binding [99mTc]NaTcO4, since nearly all DNA damage caused by [99mTc]NaTcO4 was prevented by DMSO. We prepared a 99mTc-complex with an optimal distance between the [99mTc]Tc(CO)3-core and the pyrene residue to position the 99mTc in close proximity to the plasmid DNA to induce direct SSB and DSB. By increasing the distance between the DNA-intercalating moiety and the bonding moiety for 99mTc, we observed decrease of direct DNA damages. This distance dependence has not been reported for 99mTc until now. Clinical relevant Auger electron therapy is hampered by the prerequisite of DNA binding which is hindered by cell and nucleus membranes.

Keywords: 99mTc; Auger; DNA damage; Therapy

  • Poster
    22nd International Symposium on Radiopharmaceutical Sciences (ISRS 2017), Dresden, 14.-19.05.2017, Dresden, Deutschland
  • Open Access Logo Journal of Labelled Compounds and Radiopharmaceuticals 60(2017)S1, S365
    DOI: 10.1002/jlcr.3508
    Cited 3 times in Scopus

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Publ.-Id: 26072