A Monte Carlo study of energy deposition at the sub-cellular level for application to targeted radionuclide therapy with low-energy electron emitters

Optimizing targeted radionuclide therapy for patients with circulating malignant cells (e.g. blood-related cancers) or a micrometastatic spread requires quantification of various dosimetric parameters at the single-cell level. We present results on the energy deposition of monoenergetic electrons of initial energy from 100 eV to 20 keV - relevant to Auger emitting radionuclides - distributed either uniformly or at the surface of spherical volumes of radii from 10 nm to 1 mu m which correspond to critical sub-cellular targets. Calculations have been carried out by our detailed-history Monte Carlo (MC) code which simulates event-by-event the complete slowing down (to 1 Ry) of both the primary and all subsequent generations of electrons, as well as, by the continuous-slowing-down-approximation (CSDA) using analytic range-energy relationships. The latter method has been adopted by the MRD committee of the Society of Nuclear Medicine for dosimetry at the cellular level (>1 mu m). Differences between the MC and CSDA results are up to similar to 50% and are expected to be even larger at higher energies and/or smaller volumes. They are attributed to the deficiencies of the CSDA method associated with the neglect of straggling and delta-ray transport. The results are particularly relevant to targeted radiotherapy at the genome level by Auger emitters. (c) 2007 Elsevier B.V. All rights reserved

Single-cell dosimetry for radioimmunotherapy of B-cell lymphoma patients with special reference to leukemic spread

Aims: Many lymphoma patients have both macroscopic tumors and single-cell manifestations of their disease. Treatment efficacy could, therefore, depend on the radionuclide used. The aim of this study was to investigate dosimetry at a cellular level for three isotopes of radioiodine. Methods: Cells were assumed to be spherical with radii of 6.35, 7.7, and 9.05 mu m corresponding to the dimensions of the Raji cells. The radius of the nucleus was assumed to be 75% of the cellular radius. The electron energies were 18, 28, and 190 keV, corresponding to the mean electron energy per decay for I-125, I-123, and I-131, respectively. S-values for different activity distributions were simulated using Monte Carlo and dose-volume histograms as well as absorbed doses, and absorbed dose rates were calculated. Results: I-125 gives the highest absorbed dose (similar to 4-40 times that of I-131), whereas I-123 Will give the highest absorbed dose rate (similar to 100 times that of I-131). Under the given assumptions, the absorbed dose at this level is more dependent on the Size of the cells than on whether the radioimmunoconjugate is internalized. Conclusions: This enquiry showed that both I-123 and I-125 have greater potential than I-131 for the treatment of leukemic spread in patients With lymphoma

Subcellular S-factors for low-energy electrons: A comparison of Monte Carlo simulations and continuous-slowing-down calculations

PURPOSE: To study the energy deposition by low-energy electrons in submicron tissue-equivalent targets by comparing two widely used methodologies, namely, the continuous-slowing-down-approximation (CSDA) convolution integral and the Monte Carlo (MC) simulation. METHODS: An MC track-structure code that simulates collision-by-collision the complete slowing down process is used to calculate the energy deposition in spherical volumes of unit density water medium. Comparisons are made with calculations based on the CSDA convolution integral using both empirical and MC-based range-energy analytic formulae. RESULTS: We present self-irradiation absorbed fractions and S-factors for monoenergetic electrons of initial energies from 0.1-10 keV distributed uniformly in spheres of 5, 10, 50, 100, 500, and 1000 nm radius. The MC and CSDA results were found, in some cases, to differ by a factor of 2 or more; differences generally increase with decreasing sphere size. Contrary to high energies, the uncertainties associated with the straight-ahead approximation implicit in the CSDA calculations are of the same order as those related to straggling and delta-ray effects. CONCLUSION: The use of the CSDA methodology may be unsuitable for the sub-micron scale where a more realistic description of electron transport becomes important