Verification of GEANT4-DNA and a simplified DNA model

Abstract

Cancer is becoming the second leading cause of death in the world, thus the development of effective treatment for cancer is important. Radiation therapy is a method of treating tumors using ionizing radiation to kill cancer cells. Diffusing Alpha-emitters Radiation Therapy(DaRT) is a insert radiotherapy technique in which radiogen containing 224Ra are inserted into solid tumors. The decay of the 224Ra initiates a series of alpha emissions. The alpha-particles will travel through the cells and damage the DNA. Due to the diffussion of the daughter nuclei, a reasonably sized volume of tumour tissue will be treated by each seed.

This work presents a water phantom model to analyse the deposited energy distribution by the alpha-decay chains in DaRT. The presented work focuses on the verification of Geant4-DNA results obtained at the very short distances needed for the simulation of the224Ra decay chain. The results show that even at these small scales the energy loss is modeled accurately. The structural complexity of DNA in cells often makes it difficult to fit into ordinary computer simulations, so it is necessary to construct simplified models of particle damage to cells wherever possible, not only to reduce simulation time but also to improve simulation efficiency. The Geant4-DNA toolkit has been used to study biological effects induced by ionizing radiation on tumors in this work. The structure of DNA has been used to create a simplified DNA geometry model. This work focuses on the strand breaks changes by changing the density of chromatin fibers. Indirect and direct strand breaks; single, double strand breaks are reported. From the results, it follows that the killing distance is the main parameter determining the number of indirect strand breaks. When the distance between two chromatin fibers is larger than the killing distance, then the number of indirect strand breaks will remain constant while if it is smaller the number will decrease. Therefore, the effect of chromatin fiber spacing on DNA reactivity should also be considered in simulation discussions of complex DNA models.

Date of Award	6 Dec 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Jaap J Velthuis (Supervisor)