Jiri Stepanek

Weanling piglet cerebellum: a surrogate for tolerance to MRT (microbeam radiation therapy) in pediatric neuro-oncology

The cerebellum of the weanling piglet (Yorkshire) was used as a surrogate for the radiosensitive human infant cerebellum in a Swiss-led program of experimental microbeam radiation therapy (MRT) at the ESRF. Five weanlings in a 47 day old litter of seven, and eight weanlings in a 40 day old litter of eleven were irradiated in November, 1999 and June, 2000, respectively. A 1.5 cm-wide x 1.5 xm-high array of equally space approximately equals 20-30 micrometers wide, upright microbeams spaced at 210 micrometers intervals was propagated horizontally, left to right, through the cerebella of the prone, anesthetized piglets. Skin-entrance intra-microbeam peak adsorbed doses were uniform, either 150, 300, 425, or 600 gray (Gy). Peak and inter-microbeam (valley) absorbed doses in the cerebellum were computed with the PSI version of the Monte Carlo code GEANT and benchmarked using Gafchromic and radiochromic film microdosimetry. For approximately equals 66 weeks [first litter; until euthanasia], or approximately equals 57 weeks [second litter; until July 30, 2001] after irradiation, the littermates were developmentally, behaviorally, neurologically and radiologically normal as observed and tested by experienced farmers and veterinary scientists unaware of which piglets were irradiated or sham-irradiated. Morever, MRT implemented at the ESRF with a similar array of microbeams and a uniform skin-entrance peak dose of 625 Gy, followed by immunoprophylaxis, was shown to be palliative or curative in young adult rats bearing intracerebral gliosarcomas. These observations give further credence to MRTs potential as an adjunct therapy for brain tumors in infancy, when seamless therapeutic irradiation of the brain is hazardous.

Auger-Electron Spectra of Radionuclides for Therapy and Diagnostics

The present paper documents the calculation of radiation spectra and of radial dose distribution around a point source for 24 selected radionuclides. The radionuclides were ordered into three groups: Nuclides potentially useful for therapy by emission of Auger electrons: 51Cr, 64Cu, 67Ga, 73Se, 75Se, 77Br, 80mBr, 94Tc, 99mTc, 114mIn, 115mIn, 123I, 124I, 125I, 167Tm, 193mPt, and 195mPt, nuclides potentially useful for therapy by alpha-particles with additional emission of Auger electrons: 212Bi, 211At and 255Fm, and nuclides potentially useful for electron Auger-therapy with simultaneous PET diagnosis: 73Se, 94Tc and 124I. The calculations imply strongly the development of labelled DNA-seeking compounds useful as carrier for the Auger- and Coster-Kronig electron-emitting radionuclides.

Methods to determine the fluorescence and Auger spectra due to decay of radionuclides or due to a single atomic-subshell ionization and comparisons with experiments.

The aim of this work is to describe methods of determining the fluorescence and Auger spectra due to decay of radionuclides or a single atomic-subshell ionization. First discussed is the electron vacancy generation in an atomic subshell by ionization, internal-conversion decay, or electron-capture decay. Later discussed is the status of electron vacancy following emission of fluorescence x rays and Auger electrons. Special attention is given to the relaxation probabilities and the procedures to calculate energies of released electrons. Also discussed are the Monte Carlo and deterministic methods to calculate vacancy cascades.

A program to determine the radiation spectra due to a single atomic-subshell ionisation by a particle or due to deexcitation or decay of radionuclides

Abstract The computer program IMRDEC has been developed to determine the radiation spectra due to a single atomic-subshell ionisation of a stable atom by a particle, or due to the atomic deexcitation or decay of nuclides. The data needed to describe the deexcitation or decay scheme of the mother atoms are obtained from the Evaluated Nuclear Structure Data File (ENSDF) maintained at Brookhaven National Laboratory; this results in the simplest possible input specification. The atomic data as well as the atomic relaxation probabilities are taken from the Evaluated Atomic Data Library (EADL) from Lawrence Livermore National Laboratory. The program IMRDEC calculates the radiation spectra (inclusive the atomic relaxation cascades) optionally, using the deterministic or the Monte Carlo method. The deterministic method results in a much shorter calculation time per nuclide. Due to the many assumptions that worldwide still have to be made in determining the atomic relaxation probabilities as well as in calculating the atomic relaxation, the deterministic method seems to be a small source of inaccuracy.

Radiation Spectra of 111In, 113mIn and 114mIn

The radiation spectra of 111In, 113mIn, and 114mIn are calculated with the Monte Carlo computer program IMRDEC. The relaxation probabilities are taken from the EADL file of the Lawrence Livermore National Laboratory. Because this file does not include data for some N and O transitions, these were additionally determined by applying the Kassis rule. Two schemes are applied to calculate the transition energies: 1) a simple (Z + 1)/Z scheme, and 2) accurate calculation solving the relativistic Dirac equations. It is shown that using the extended set of relaxation probabilities leads to generation of many additional low-energy Auger and CK electrons if the (Z + 1)/Z rule is applied. On the other hand, the emissions of almost all these electrons are rejected if their energies are calculated solving the Dirac equations taking into consideration realistic electron vacancies.

Comparison of different cell-cluster models for cell-level dosimetry

An important factor in dose calculations for targeted radionuclide therapy is the cell-cluster model used. We developed a cell-cluster model based on optimization through mechanical hard-sphere collisions. The geometrical properties and the dosimetric effects of the new model were compared with those of two previous models, i.e. the traditional lattice model and our CellPacker model in which the cells are individually and systematically piled as a cluster. The choice of the cell-cluster model has an effect on the calculated mean absorbed doses in the cells. While CellPacker produces clusters with distinct tumour-healthy tissue interface, our new model is able to make the interface diffuse. Outside the interface the new model is capable to pack cells tighter than CellPacker enabling the description of tissues of higher cellular density. Our two cluster models make it possible to construct the cluster model according to the tissue in question.An important factor in dose calculations for targeted radionuclide therapy is the cell-cluster model used. We developed a cell-cluster model based on optimization through mechanical hard-sphere collisions. The geometrical properties and the dosimetric effects of the new model were compared with those of two previous models, i.e. the traditional lattice model and our CellPacker model in which the cells are individually and systematically piled as a cluster. The choice of the cell-cluster model has an effect on the calculated mean absorbed doses in the cells. While CellPacker produces clusters with distinct tumour-healthy tissue interface, our new model is able to make the interface diffuse. Outside the interface the new model is capable to pack cells tighter than CellPacker enabling the description of tissues of higher cellular density. Our two cluster models make it possible to construct the cluster model according to the tissue in question.

A Deterministic Method to Calculate the Radiation Spectra of Nuclides

Recently, the computer program IMRDEC has been developed to determine the radiation spectra due to a single atomic-subshell ionisation of a stable atom by a particle, or due to the atomic deexcitation or decay of nuclides. The data needed to describe the deexcitation or decay scheme are obtained from the Evaluated Nuclear Structure Data File (ENSDF) maintained at Brookhaven National Laboratory; this results in the simplest possible input specification. The atomic data as well as the atomic relaxation probabilities are taken from the Evaluated Atomic Data Library (EADL) from Lawrence Livermore National Laboratory. The program IMRDEC calculates the radiation spectra (inclusively the atomic relaxation cascades) deterministically rather than by the Monte Carlo method; this results in much shorter calculational time per nuclide. Since many assumptions still have to be made in determining the atomic relaxation probabilities and in calculating the atomic relaxation, the deterministic method seems to be a small source of inaccuracy.

Emission spectra of Gadolinium-158

The photon and electron spectra of 158*Gd as result of the (n, gamma)-reaction on 157Gd were calculated with IMRDEC Monte Carlo computer program. The relaxation probabilities were taken from EADL file of the Lawrence Livermore National Laboratory. Because this file does not consist of data for some N and O transitions, they were additionally determined by Chen applying the DHS j-j scheme. Two schemes are applied to calculate the energies of the transitions: (1) a simple (Z + 1)/Z scheme, and (2) accurate calculation solving the relativistic Dirac equations.

Cluster Models in Cellular Level Electron Dose Calculations

A program for calculating absorbed dose was developed for radioimmunotherapy (RIT) purposes. It was used to determine the difference in the therapeutic effect of (111)In electrons when using a close-packed cubic geometry and a cell cluster model developed in this project. Our cluster model piles the cells individually. The cells were modelled as spheres of diameters of 12 (tumour) and 30 (healthy) microm. Both models were used to generate clusters with spherical tumours inside healthy tissue. The program uses Monte Carlo-based dose kernels. The radiation spectra were calculated from the Auger and x-ray transition strengths and fluorescence yields of (111)In. The results show the importance of the cluster model in cellular level dose calculations. Near the tumour/healthy tissue interface in particular, the doses differ because of geometrical differences. In the case of a small cluster with tumour and total diameters of 30 and 150 microm, the ratio of the therapeutic effects is 20.

Future electron accelerators and free electron lasers: Potentials in clinical medicine

Abstract Studies of the biological and technical prerequisites for the clinical use of monoenergetic X-rays, and their specific absorption in heavy elements are conducted, with a view towards plans for stereotactic photon activation radiosurgery. The primary aim is the controlled eradication of target structures in the brain for the treatment of functional brain disorders or small brain tumours, with monochromatic synchrotron X-rays. The specific cell-killing action is based on DNA-breakage caused by short-range Auger and Coster-Kronig electrons produced by heavy atoms upon K-shell absorption of their characteristic X-rays. To this end, iodine or heavy metals would have to be deposited, in or close to nuclear DNA in target cells by means of suitable molecular vehicles. Practically useful concepts for clinically useful monoenergetic X-ray facilities and beam-lines are being developed. In this paper attention is focussed on the possible use of laser Compton backscattering for the production of clinically useful monochromatic X-ray beams suitable for irradiation of very small targets in the brain through the intact skull. Particularly relevant, in the present context are prospects for introducing free electron laser technology to improve the calculated parameters of X-ray beams designed for stereotactic photon activation radiosurgery with monochromatic photons in the energy interval 30–100 keV. Constructive initiatives would be welcome!