Microdosimetry Analysis And Biological Effect Prediction Based On Mesh-type Cell Model Of Prostate Cancer

As a common malignant tumor,prostate cancer can be controlled by surgery、chemotherapy、radiotherapy and other means.Treatment with radionuclide labeled prostate specific membrane antigen(PSMA)has been shown to be a safe,effective,and promising approach for the treatment of metastatic castration-resistant prostate cancer.Numerous basic and clinical studies have demonstrated the efficacy of 177Lu and 225Ac labeled PSMA to achieve tumor-targeted radioligand therapy for prostate cancer,respectively.From the perspective of radiation dosimetry,the biological effects of radiation in clinic are derived from the energy transfer of ionizing radiation at cellular and subcellular scales,and the deposition characteristics of microscopic energy are closely related to radiation quality.Therefore,microdosimetric quantitative analysis at the cellular level is of reference significance for understanding the biological effects of radiation induced by radiation of different radiation qualities.From ionizing cluster and DNA damage prediction in nanodosimetry to line energy and proximity function in microdosimetry,these indicators can be used as the basis to evaluate radiation quality,so as to further predict biological effects such as cell survival rate and tumor control probability at macro level.Monte Carlo(MC)method,as one of the main theoretical means to simulate the interaction between radiation particles and biological media,can restore the tracks of radiation particles.In particular,the Track Structure(TS)transport model which was more refined than the Condensed History(CH)model was more suitable for the study of micro and nano dosimetry.In addition,because the micro-scale energy deposition is greatly affected by the size and shape factors of sensitive sites,the cell curved surface model can highly restore the real cell morphology,and is a powerful tool for accurate quantification of cell dose.Therefore,on the basis of combining microdosimetry theory and Monte Carlo method to clarify the physical properties of different types of radiation particles,combined with the cell curved model of prostate cancer can help to quantify the microdosimetry distribution of cell clusters and predict their biological effects.Firstly,based on the study of ray quality,this paper studies the difference of microdosimetric proximity functions caused by various physical configurations.Based on TS model and CH model,a variety of Monte Carlo models(Geant4-DNA,PHITS,Penelope)were selected to simulate the track structure of low energy electrons in liquid water,and the effects of initial energy,cut-off energy,energy spectrum and physical model on the differential Proximity function were evaluated.Using 10 keV single energy electron as standard radiation,the relative biological effects of electrons,protons and α particles with different initial energies were estimated and analyzed.This work comprehensively compares the inherent differences of various physical configurations by setting different transport control conditions,which has basic guiding significance for helping users to select appropriate physical configurations to simulate various particles according to their needs,improves the microdosimetry database of charged particles in liquid water,and provides a strong basis for evaluating the biological effects of ionizing radiation at the microscopic scale.Secondly,based on confocal laser microtomography images,a single prostate cancer curved surface model and its 3D cell cluster model were constructed in vivo.The effects of cell shape,22Ac and 177Lu nuclide distribution and mixing ratio on microdosimetric distribution of cell clusters and the resulting tumor control probability(TCP)were estimated and analyzed based on Geant4.The results of Geant4 simulation were compared with the cell clusters composed of concentric circles by MIRDcell software.The relationship between nuclide activity,cell dose and TCP was established to provide theoretical reference for the dosimetry of mixed nuclides in clinical treatment of castration-resistant prostate cancer.In this paper,a variety of measures of microdosimetry and macrodosimetry,combined with a curved mesh-type model and a variety of Monte Carlo software,have solved the problem that it is difficult to quantify the relative biological damage effects of rays of various energies.Meanwhile,the activity dose TCP curve has been established,which provides a basis for in-depth understanding of the injury characteristics of 225Ac and 177Lu and for the clinical application of nuclide mixing.