Microdosimetry Study for Targeted Radiotherapy

Ionizing radiation is currently one of the most successful therapeutic modalities in oncology. Traditional external beam radiotherapy makes use of a treatment plan to shape the beam to match the target volume, i.e. to maximize the tumor dose and to minimize the normal tissue dose. However, this radiotherapy takes no advantage of the biologically selective delivery of radiation doses to cellular or sub-cellular target regions. Targeted radiotherapy, or cell-directed radiotherapy, refers to the selective delivery of radiation doses to pathological cells leading to an enhanced therapeutic ratio. Such radiotherapy is a growing modality of tumor treatment due to the development of new biological targeting agents. The aim of the targeted radiotherapy is to use radionuclides which have high LET (linear energy transfer) particle emissions conjugated to appropriate carrier molecules. Typical examples include the anti-gene radiotherapy, involving DNA conjugated Auger electron emitters, and the boron neutron capture therapy (BNCT), applying alpha particles and heavy ions. Theoretically, targeted radiotherapy has several advantages over conventional radiotherapy since it results a high radiation dose from high LET particles administered without causing normal tissue toxicity. Although there are limitations in the availability of appropriate targeting agents and in the calculations of administered doses, clinical applications of targeted radiotherapy is still in good progress. In this project, the potential use of targeted tumor radiotherapy will be surveyed. General aspects and considerations, such as the potential radionuclides and the mechanisms of tumor targeting, will be reviewed. Microdosimetry and nanodosimetry for the cellular and the sub-cellular radiation dose and biological effectiveness will be studied. For theoretical investigations, cellular and DNA models will be developed. Monte Carlo simulations will be carried out to study the cellular S-value, the lineal energy, and the yield of DNA single- and double-strand breaks. For experimental investigations, the microdosimetric TEPC (tissue equivalent proportional counter) will be used to measure the cellular dose distribution versus lineal energy. Thus, the cellular S-value and the RBE (relative biological effectiveness) can be determined and then compared with theoretical results. Clinical applications will be sought.

Project ID:PC9801-1816
External Project ID:NSC96-2321-B182-006-MY3