Hindawi Publishing Corporation Computational and Mathematical Methods in Medicine Volume 2012, Article ID 153212, 6 pages doi:10.1155/2012/153212 Research Article Microdosimetry for Targeted Alpha Therapy of Cancer Chen-Yu Huang, 1 Susanna Guatelli, 2 Bradley M. Oborn, 2, 3 and Barry J. Allen 4 1 Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, NSW 2217, Australia 2 Illawarra Cancer Care Centre, Wollongong, NSW 2522, Australia 3 Centre for Medical Radiation Physics, University of Wollongong, NSW 2522, Australia 4 Ingham Institute of Applied Medical Research, Faculty of Medicine, University of Western Sydney, Liverpool, NSW 2170, Australia Correspondence should be addressed to Chen-Yu Huang, cyhuangsysu@gmail.com Received 3 July 2012; Accepted 25 July 2012 Academic Editor: Eva Bezak Copyright © 2012 Chen-Yu Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Targeted alpha therapy (TAT) has the advantage of delivering therapeutic doses to individual cancer cells while reducing the dose to normal tissues. TAT applications relate to hematologic malignancies and now extend to solid tumors. Results from several clinical trials have shown efficacy with limited toxicity. However, the dosimetry for the labeled alpha particle is challenging because of the heterogeneous antigen expression among cancer cells and the nature of short-range, high-LET alpha radiation. This paper demonstrates that it is inappropriate to investigate the therapeutic efficacy of TAT by macrodosimetry. The objective of this work is to review the microdosimetry of TAT as a function of the cell geometry, source-target configuration, cell sensitivity, and biological factors. A detailed knowledge of each of these parameters is required for accurate microdosimetric calculations. 1. Introduction Targeted alpha therapy (TAT) can provide selective systemic radiotherapy to primary and metastatic tumors (even at a low dose rate and hypoxia region) [1]. It permits sensitive discrimination between target and normal tissue, resulting in fewer toxic side effects than most conventional chemothera- peutic drugs. Monoclonal antibodies (MAbs) that recognize tumor-associated antigens are conjugated to potent alpha emitting radionuclides to form the alpha-immunoconjugate (AIC) (Figure 1). The AIC can be administered by intra- lesional, orthotopic, or systemic injection. Targeted cancer cells are killed by the short-range alpha radiation, while spar- ing distant normal tissue cells, giving the minimal toxicity to normal tissue [2]. An alpha particle with energy of 4 to 9 MeV can deposit about 100 keV/μm within a few cell diameters (40–90 μm), causing direct DNA double-strand breaks, which lead to cancer cell apoptosis [3]. Cell survival is relatively insensitive to the cell cycle or oxygen status for alpha radiation [4]. TAT is potent enough to eradicate disseminated cancer cells or cancer stem cells that are minimally susceptible to chemo- or radio-resistance. The relative biological effect (RBE) of alpha particles is from 3 to 7 [5], which means that for the same absorbed dose, the acute biological effects of alpha particles are 3 to 7 times greater than the damage caused by external beam photons or beta radiation. TAT is ideally suited to liquid cancers or micrometastases [6]. However the regression of metastatic melanoma lesions after systemic TAT in a phase I clinical trial for metastatic melanoma has broadened the application to solid tumors [7]. The observed tumor regression could not be ascribed to kill- ing of all cancer cells in the tumors by TAT and led to the hypothesis that tumors could be regressed by a mecha- nism called tumor antivascular alpha therapy (TAVAT) [8]. Therapeutic efficacy relates to the extravasation of the AIC through porous tumor vascular walls and widened endo- thelial junctions into the perivascular space in the solid tumor. The AICs bind to antigenic sites on the membranes of pericytes and contiguous cancer cells around the capillary. The alpha-particle emitters are localized close to the vascular endothelial cells (ECs), which are irradiated by alpha parti- cles and killed. Subsequent tumor capillary closure, causing