Microdosimetry Study of Advanced Radiotherpy

The use of densely ionizing particles in radiotherapy will become popular in Taiwan. The Linko Chang Gung Memorial Hospital is installing the first proton therapy facility in Taiwan. Several other hospitals also showed their interest in practicing the proton or carbon ion therapy. In collaboration with National Tsing Hua University, the Taipei General Veterans Hospital is applying for clinical trials of the boron neutron capture therapy (with alpha particles and lithium ions). Further, in Europe, Japan and United States the photon activation therapy using targeted platinum loaded drugs is under intensive study. One of the advantages of applying densely ionizing particles in radiotherapy is their high specific energy depositions in tumor cells. In other words, under equal absorbed dose the probability of DNA double strand breaks by these particles is larger than that by photons and electrons. For radiotherapy using densely ionizing particles, radiation dose should be prescribed with lineal energy weighting biological dose (in units of GyE) rather than physical dose (in units of Gy). Since RBE values depend on the cellular microdosimetry and DNA nanodosimetry, the study of densely ionizing particle radiotherapy is important in clinical applications and academic research. In this project, a study of the cellular microdosimetry and DNA nanodosimetry is proposed for densely ionizing particle therapies, i.e. proton, carbon ion, and photon activation therapies. With this study, the biological doses of these treatment modalities will be evaluated. The proposed study will develop theoretical methods and experimental techniques for the calculations and measurements of beamlines in the densely ionizing particle radiotherapy. These beamlines will be used to determine the dose-weighted lineal energy distribution, D(y), for tumor and normal cells at different locations in the phantom or the body. Combining with the biological weighting function, R(y), the effective RBE will be determined. Further, the biological doses in the prescription and treatment planning will be obtained. Methods to be adopted in the study include (1) the use of Monte Carlo (MC) transport code to simulate the densely ionizing particle beamlines for calculations of the absorbed dose contributed from all secondary particles produced in the phantom or the body, (2) the development of a MC microdosimetry program to simulate the cellular dose from densely ionizing particle beamlines, (3) the development of a MC nanodosimetry program to simulate the DNA dose from densely ionizing particle beamlines, (4) the design and fabrication of a mini tissue equivalent proportional counter (TEPC) for measurements of the dose-weighted lineal energy distribution, D(y), (5) the design and fabrication of an SOI (silicon on insulator) microdosimeter for measurements of the dose-weighted lineal energy distribution, D(y), (6) the study of biological weighting functions, R(y), for different cells and biological endpoints, and (7) the study of DNA double strand break yields induced by Auger electrons emitted from the photon activation therapy. Over the years, the PI of this project has made extensive study on the microdosimetry and nanodosimetry for different applications. Various theoretical methods and experimental techniques have been developed, e.g. MC simulations of the cellular S-value, MC simulations of the DNA double strand break, experimental measurements using the TEPC for BNCT, etc. Several publications and invited talks were resulted from such a study. The experience obtained in this study should be of great help in carrying out the proposed study of this project. After modifications, several previously developed programs and instruments can be used in the present study. A three-year project is proposed. Results from this study can be readily applied in clinical radiotherapy. Skills and technologies developed for the densely ionizing particle radiotherapy in microdosimetry and nanodosimetry measurements and simulations can be appreciated. Graduate students will be trained comprehensively during their study.

Project ID:PC9907-0700
External Project ID:NSC99-2314-B182-041