Frontiers in Physics (Nov 2020)
Estimating the Relative Biological Effectiveness of Auger Electron Emitter 123I in Human Lymphocytes
Abstract
Auger electron emitters are considered to be a promising strategy for targeted radionuclide therapy of metastatic diseases, given their high linear energy transfer (LET) and short range in tissue which could potentially limit normal tissue toxicity. Particularly Auger electron emitters that can be targeted into the DNA of tumor cells have been considered as an attractive cancer therapy in the past decade. In this study, the efficiency of the Auger electron emitter 123I (half-life 13.2 h) to induce chromosomal damage was investigated by using the cytokinesis-block micronucleus assay. A stannylated deoxyuridine was synthesized and radiolabeled with 123I, resulting in 123IUdR that carried the Auger electron emitter across the nuclear membrane and allowed its incorporation into newly synthesized DNA. The DNA damage caused by the 123I Auger cascade was estimated by evaluating the induced micronuclei frequencies in human peripheral blood lymphocytes obtained from three different donors. The isolated lymphocytes were stimulated with phytohemagglutinin (1 mg/ml) for 48 h before pulse labeling with 123IUdR and the S-phase fraction was determined using flow cytometry. Geant4 Monte Carlo calculations were performed to determine the absorbed dose in cells by the Auger emitter. The relative biological effectiveness (RBE) was calculated by comparing the dose response curves for 123IUdR with the reference dose response curves, obtained with 60Co γ-ray irradiation in this study, for lymphocytes of the same donors. This resulted in a range of individual RBE values from 3 up to 10, depending on the donor and the radiation dose. In addition, dose limiting RBE values (RBEMax) were calculated for each donor and ranged from 5 to 11, dependent on the inherent radiosensitivity of the donors. This study provides valuable information on the RBE of Auger electron emitter 123I, which is identified as a promising theranostic radionuclide for future targeted radionuclide therapy.
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