ACRIDINE ORANGE DERIVATIVES AS DNA-TARGETED RADIOPHARMACEUTICALS FOR AUGER THERAPY
Targeted therapy with Auger electron-emitting radionuclides has emerged as a promising approach to molecular radiotherapy. Continuing our previous work on acridine orange (AO) derivatives as DNA-targeted tools for Auger therapy, we have found that the radioprobes 125I-C5 and 99mTc-C3 place the corresponding radionuclide at relatively similar distances to DNA (ca 10 Å) and produce comparable DSB yields in plasmid and cellular DNA. This is the first evidence that 99mTc can induce DNA damage with an efficiency similar to that of 125I, when both radionuclides are placed at comparable distances to the double helix. Furthermore, 99mTc-C3 presents a higher retention in the nucleus of tumoral cells than than 125I-C5, which suggests that 99mTc-labeled AO derivatives are better tools for the design of Auger-emitting radiopharmaceuticals than the 125I-labeled congeners.
Contact Person: António Paulo
More details in
Pereira, E et al. (2017) Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA, Scientific Reports 7, 42544, doi:10.1038/srep42544.