The energy imparted to biological tissue after the decay of incorporated Auger emitters stems from two sources: (a) energy deposition by the Auger and Coster-Kronig electrons and (b) the charge potential which remains on the multiple ionized atom after the end of the cascade. For the numerical assessment of both the kinetic energy of the released electrons and the charge potential, a new and--for purposes of microdosimetry--precise method is presented. Based on relativistic Dirac-Fock calculations and a rigorous bookkeeping, this method provides a perfect energy balance of the considered atomic system when applied to Monte Carlo simulations of Auger cascades. By comparing the results for charge distribution for krypton and iodine with experimental data and the electron spectrum of 125I with theoretical data, it can be shown that the approach followed in this work is reasonable and appropriate for the determination of the energy deposited by incorporated Auger emitters in small volumes of condensed matter. The total energy deposited by 125I in a volume of 20-nm diameter is 2.03 keV which is made up by multiple ionization (1.07 keV) and energy deposition by the emitted Auger electrons (0.96 keV).

A DNA target model has been developed, based on the geometrical co-ordinates of individual atoms. This model is used to analyse DNA damage produced by Auger electron tracks from the decay of 125I. The high resolution of this target model enables the distinction between direct and indirect electron hits, i.e. hits inside the atomic volumes of the DNA molecule and those hitting the water molecules assumed in the space between the atomic volumes. Three types of calculations have been performed: (1) the evaluation of the energy deposition in the surroundings of the decaying 125I nuclide demonstrating different fractions of direct to indirect hits at different parts of the DNA molecule (phosphate/sugar strand or bases), (2) a detailed energy deposition pattern in the radiolabelled base, indicating that this most burdened molecule is not necessarily destroyed by direct hits, and (3) a calculation of single- and double- strand breaks by using different threshold values for effective direct and indirect hits, resulting in a good correlation with experimental data on strand break efficiency.

Understanding the strong radiotoxicity of DNA-incorporated Auger electron-emitting nuclides requires a detailed knowledge of the nuclide's emission spectrum. A Monte Carlo computer code was previously developed to simulate Auger cascades and to provide electron spectra of 125I. To utilize experimental data for a direct validation of these simulations, the code has been adapted for cascades in xenon, which is adjacent to iodine in the table of elements. Only minor modifications of the code were necessary to obtain a very good agreement with the experimental findings. The role of shake-off electrons and the need for energy considerations during the cascades could be demonstrated. A previously published electron spectrum of 125I was recalculated and detailed results are presented here. Furthermore, to consider implications from a molecular binding of the Auger emitter, for the first time semi-empirical quantum mechanical calculations for an iodine-labelled thymine molecule were performed showing that even in the condensed phase a Coulomb explosion cannot be excluded a priori.

This paper is a contribution to the microdosimetry of I-125. It shows microdosimetric spectra of individual and average disintegrations of I-125 for various target sizes and gives evidence for the relative contributions of energy-deposition events of low and high LET. It further presents information on the relative efficiencies of Auger-electrons and multiple charges in terms of local energy deposition, e.g. to model targets of DNA, and discusses their radiobiological implications, e.g. the microdosimetric understanding of the different efficiencies of specific and random incorporations of I-125. When I-125 is specifically incorporated into DNA, most of the energy deposition events are very large, e.g. above 40 keV/micron for a simulated target volume of 20 nm diameter, regardless of the number and energy of Auger electrons emitted. Therefore it is not necessary, for the discussion of the radiobiological implications, to distinguish between different classes of disintegrations. For unspecific, homogeneous incorporation of I-125 somewhere into tissue, about 20% of the dose to critical targets of 25 nm diameter is made up by disintegrations that happen to occur within these targets. When assuming that other critical targets and target structures can be neglected, this part of the dose will be equally effective as in the case of specific incorporation of I-125 into such target models. In addition, there are the normal, low-LET radiation effects from the other, 80% large fraction of the dose. With this information, for the biological systems and end points for which a short section of the elemental chromatine fiber can be taken as the relevant critical target, it is shown that the expected D37 value for homogeneous unspecific incorporation of I-125 can be estimated when the D37 for specific incorporation in DNA is known. For an example calculation, the estimated D37-value for nonspecific, homogeneous incorporation of I-125 would be about half as effective as specifically incorporated I-125. Thus, the microdosimetric data of the present work show that a high efficiency of homogeneous incorporation of I-125 into the cell nucleus is not necessarily in contradiction with the idea of I-125 disintegrations inside the DNA being the main cause of radiation action.