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.

[1]  D. Emfietzoglou,et al.  An event-by-event computer simulation of interactions of energetic charged particles and all their secondary electrons in water , 2000 .

[2]  J. Kereiakes,et al.  Auger electron dosimetry: report of AAPM Nuclear Medicine Committee Task Group No. 6. , 1992, Medical physics.

[3]  A. Kassis The MIRD approach: remembering the limitations. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  M. Kaminski,et al.  Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Kostas Kostarelos,et al.  A Monte Carlo track structure code for electrons (~10 eV-10 keV) and protons (~0.3-10 MeV) in water: partitioning of energy and collision events , 2000 .

[6]  A. Cole Absorption of 20-eV to 50,000-eV electron beams in air and plastic. , 1969, Radiation research.

[7]  P. Zanzonico,et al.  Internal radionuclide radiation dosimetry: a review of basic concepts and recent developments. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  G T Chen,et al.  Microdosimetric concepts in radioimmunotherapy. , 1993, Medical physics.

[9]  C. Punt,et al.  Clinical applications of newer radionuclide therapies. , 2006, European journal of cancer.

[10]  B. Cheson,et al.  Response criteria for NHL: importance of 'normal' lymph node size and correlations with response rates. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[11]  J. Humm,et al.  A new calculational method to assess the therapeutic potential of Auger electron emission. , 1989, International journal of radiation oncology, biology, physics.

[12]  Hooshang Nikjoo,et al.  The Effect of Model Approximations on Single-Collision Distributions of Low-Energy Electrons in Liquid Water , 2005, Radiation research.

[13]  R. Howell The MIRD Schema: from organ to cellular dimensions. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[14]  A. Ballangrud,et al.  Liposome-mediated radiotherapeutics within avascular tumor spheroids: comparative dosimetry study for various radionuclides, liposome systems, and a targeting antibody. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  S. Strand,et al.  Internal microdosimetry for single cells in radioimmunotherapy of B-cell lymphoma. , 2005, Cancer biotherapy & radiopharmaceuticals.

[16]  L. Gordon,et al.  Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  E. Cavallin-ståhl,et al.  Flow cytometric light chain analysis of peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma. , 1985, British Journal of Cancer.

[18]  M G Stabin,et al.  Re-evaluation of absorbed fractions for photons and electrons in spheres of various sizes. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  Kostas Kostarelos,et al.  An analytic dosimetry study for the use of radionuclide-liposome conjugates in internal radiotherapy. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  Francis A Cucinotta,et al.  A Complete Dielectric Response Model for Liquid Water: A Solution of the Bethe Ridge Problem , 2005, Radiation research.

[21]  M. Bardiès,et al.  Computational methods in radionuclide dosimetry , 1996, Physics in medicine and biology.

[22]  M. Gaze The current status of targeted radiotherapy in clinical practice. , 1996, Physics in medicine and biology.

[23]  J. Humm,et al.  Dosimetry of Auger-electron-emitting radionuclides: report no. 3 of AAPM Nuclear Medicine Task Group No. 6. , 1994, Medical physics.

[24]  R. Vessella,et al.  Dosimetry of solid tumors. , 1993, Medical physics.

[25]  R. Howell,et al.  Macroscopic dosimetry for radioimmunotherapy: nonuniform activity distributions in solid tumors. , 1989, Medical physics.

[26]  R. Böhm,et al.  Monte Carlo Calculations of Energy Deposition in DNA for Auger Emitters , 2000 .

[27]  I. Panyutin,et al.  The potential for gene-targeted radiation therapy of cancers. , 2005, Trends in biotechnology.

[28]  T. Wheldon,et al.  Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.