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Biomedical Imaging and Instrumentation

Biomedical Imaging and Instrumentation - Poster Session E

Poster R15 - simulating alpha particle doses at the micron level using GATE from prostate cancer patient derived tissue biopsies

Saturday, October 26, 2024

10:00 AM - 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

AS

Abdulaziz Said, n/a

Graduate Student
Washington University in St. Louis
Springfield, Illinois, United States

Primary Investigator(s)

DT

Daniel L.J Thorek, PhD (he/him/his)

Associate Professor of Radiology and Biomedical Engineering
Washington University in St. Louis
Saint Louis, Missouri, United States

Co-Author(s)

JM

Justin Mikell, PhD

Assistant Professor of Radiation Oncology, Division of Medical Physics
Washington University School of Medicine, United States
Allan Thomas, PhD

Assistant Professor of Radiology
Washington University School of Medicine, United States
Isabella M. Salerno

Graduate Student
Washington University in St. Louis
Saint Louis, Missouri, United States

Introduction: Castrate resistant bone metastatic prostate cancer is a leading cause of mortality, and the disease is incurable. Consequently, much effort has been devoted in the development of targeted therapies. One such promising approach employs the use of radiation emitting ligand complexes, so called radio pharmaceutical therapies, for this purpose. Alpha particle emitting radionuclides have particularly garnered much attention due to their short path length and high linear energy transfer. These characteristics suggest the potential for alpha therapies to selectively target cancerous tissue while sparing surrounding normal tissue. Radium Dichloride is the first such alpha therapy approved for use, which provides significant benefit to patient’s overall survival. However, it has been shown that alpha particles energy deposition paths are highly susceptible to variations in the microstructure of the target region. Thus, traditional whole organ dose estimations fundamentally mischaracterize biological effects of alpha therapies. To overcome these challenges, use of simulations and pharmacokinetic modeling are important steps in the development of these therapies and stand to markedly improve understanding of biologically relevant effects. Here, we aim to further quantify dosimetry effects of radium 223 treatment at the micron level. To do so, we employ a unique approach involving Monte Carlo simulations built on real-world patient bone structure and patient derived activity distributions.

Materials and

Methods: Bone biopsies at osseus lesion sites were extracted from seven patients undergoing Radium Dichloride treatment 24 hours after administration of 55 Bq/kg of the therapy. These biopsies were then imaged using a micro-CT with high resolution (17.5 µm isotropic voxels; Supplemental Figure 1A) and subsequently utilized in the Monte Carlo simulation toolkit GATE (Geant4 Application for Tomographic EmissionV9.3). To simulate treatment with Radium 223, voxelized activity of Radium 223 was initialized on the surface of the bone according to a realistic probability distribution. The simulation architecture was built on three dimensional .MHA files, for geometry and source descriptions. Physics processes were controlled via the use of QGSP_BIC_EMZ and emstandard_opt4physics lists, as well as GATE’s radioactive decay module, to simulate the entire 223Radium decay chain. The total activity initialized per run was set to 25 Bq. Python 3.8.11 was used to generate voxelized source files and activity data files. Following the execution of the simulation, absorbed dose measures were analyzed as a function of the source distribution. Specifically, three source activity conditions were considered. Activity confined to a single voxel, activity evenly distributed within the bone surface and thirdly, Activity distributed according to a randomized pattern.

Results, Conclusions, and Discussions: Following the completion of each simulation run, absorbed dose maps were extracted. From these maps, the absorbed dose to each voxel of interest could be evaluated. For each of the three source conditions described, the resultant absorbed dose distributions were calculated and compared to its corresponding initialized activity. Supplementary Figure 1B-C depicts two examples of activity distributions employed. The resulting dose outputs from these simulations support the proposed simulation architecture. Specifically, it is noted that in conditions where the source was confined to a single voxel, the absorbed dose values are reliably noted to rapidly fall off within a 1 to 4 voxel radius of the initialized activity, with variation likely due to unique bone structure. For activity distributions two and three, we see a similar pattern in which absorbed dose values are strongly influenced by the voxel-to-voxel variation in initial activity amounts, as well as the geometrical environment directly surrounding it. Additionally, multitudes of activity distributions are able to be generated, enabling future studies analyzing effects of biologically feasible distributions on patient derived geometries.
Alpha therapies are a promising approach for targeted treatment of late stage metastatic cancers. However, there remains a limited understanding of micro and cellular level interactions of these therapies. This study provides for a framework to bridge this gap through simulations and modeling techniques. By employing imaged biopsies from patients, and realistic source distributions, reliable quantification of radiopharmaceuticals is possible, leading the way to more efficacious treatment options.

Acknowledgements (Optional):