Microdosimetry for targeted alpha therapy of cancer

Comput Math Methods Med. 2012:2012:153212. doi: 10.1155/2012/153212. Epub 2012 Sep 4.

Abstract

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.

MeSH terms

  • Alpha Particles / therapeutic use*
  • Animals
  • Cell Nucleus / metabolism
  • Computer Simulation
  • DNA Damage
  • DNA Repair
  • Humans
  • Hypoxia
  • Kinetics
  • Monte Carlo Method
  • Neoplasms / radiotherapy*
  • Radioisotopes / analysis
  • Radiometry / methods*
  • Radiotherapy / methods
  • Radiotherapy Planning, Computer-Assisted
  • Reproducibility of Results
  • Stochastic Processes

Substances

  • Radioisotopes