THE ENERGY DEPOSITION DISTRIBUTION AT THE MICRO AND NANO-SCALE FOR MOLECULAR TARGETED RADIOTHERAPY: COMPARISON BETWEEN 125I, 99MTc AND 64Cu

Given the very short range (micrometers to few nanometers) of Auger electrons (AE), Coster-Kronig (CK) and internal conversion (IC) electrons emitted by several radionuclides, they are nowadays considered as promising solutions for molecular targeted radiotherapy. The aforementioned electrons can locally deposit their energy near the radionuclide decay site, reducing the radiotoxicity of the surrounding healthy tissues in this way. 125 I (T1/2=59 days, 23 Auger electrons emitted per decay, Auger= 520 eV) and 99m Tc (T1/2=6 h, 4.4 Auger electrons emitted per decay, Auger=213 eV) are two radionuclides that are largely studied for their potential use in theranostic, even if the effectiveness of the 99m Tc Auger emissions in inducing DNA double strand break (DSB) is still controversial. However, in recent years the use of 64 Cu (T1/2=12.7 h, 1.80 Auger electrons emitted per decay, Auger=1134 eV) emerged and became a burning issue, because, in addition to its imaging capabilities, some studies showed that 64 Cu has cytotoxicity capabilities when incorporated in radiopharmaceuticals targeted at tumor cells. Therefore, for 64 Cu the accurate assessment of the energy deposition pattern near the radionuclide decay site and how this energy varies with the radionuclide-DNA center distance is of paramount importance in order to better design therapeutic strategies based on the Auger electrons emitted by this radionuclide. For this reason, the aim of this work is to study the absorbed dose in the DNA and cell volumes considering the aforementioned three radionuclides described above and for the different spectra emissions of A, CK, IC and radiation. In order to reach these goals, the state-of-the-art Monte Carlo (MC) radiation transport program MCNP6 was used. For the modeling and simulation purposes, a simplified geometry for the DNA segment, the cytoplasm and the cell, composed of liquid water, was considered and an isotropic-like source was modeled. Emission data (photons were neglected) were obtained from the International Commission on radiological Protection (ICRP) publication ICRP-107. This study shows to what extent the deposited energy pattern distribution is affected when several spectra qualities are considered (Auger, Conversion and emissions); the discussion and comparison of results (also in terms of S-values calculated in this work and reported by MIRD) obtained for 64 Cu with those obtained for 125 I and 99m Tc are reported.