Radiation and Cancer Biology

PV 03 - Poster Viewing Q&A - Session 3

TU_24_3490 - Development of a Monte Carlo-Based Microdosimetry Platform for the Analysis of Targeted Radionuclide Therapy Agents in Vitro

Tuesday, September 17
1:00 PM - 2:15 PM
Location: ASTRO Innovation Hub

Development of a Monte Carlo-Based Microdosimetry Platform for the Analysis of Targeted Radionuclide Therapy Agents in Vitro
D. Adam1, N. Schweitzer1, S. Hoffman1, and B. Bednarz2; 1University of Wisconsin, Madison, WI, 2Department of Medical Physics, University of Wisconsin, Madison, WI

Purpose/Objective(s): There is a growing need for the development of a microdosimetric modeling tools that can characterize the dosimetric impact of therapeutic radiopharmaceutical agents at the cellular scale in order to improve drug development and clinical translation. Sub-cellular characterization of dose is necessary due to the heterogeneous spatial uptake of these agents in the tumor microenvironment and the short range of their decay products, especially for alpha- and auger electron-emitting drugs. In this work we present the initial steps of characterizing a GEANT4 Monte Carlo microdosimetry platform to evaluate sub-cellular dosimetry for human ovarian cancer cells (OVCAR3) treated with Auger electron-emitting Bromine-77 labeled compounds.

Materials/Methods: OVCAR3 cells were cultured, stained with DAPI and MitoSpy-Green and then imaged on a Leica SP8 3X STED super-resolution microscope to create a Z-stack image set of a single OVCAR cell. The Z-stack image set was imported into Amira to delineate the nucleus and cytoplasm. The images and contours were then imported into a computer algorithm script that created input files for GEANT4 defining both a voxelized OVCAR3 cell phantom and a radioactive source specification. GEANT4-DNA physics definitions were utilized to ensure accurate modeling of sub-micron level dose deposition. To validate the dosimetric accuracy of the platform, cellular S-values of voxelized spheres are compared to MIRDCELL values for multiple isotopes, including Bromine-77. To demonstrate the impact of realistic geometrical definitions, the dose distribution of a uniform source distribution is compared between a realistic voxelized OVCAR cell and a voxelized sphere of an equivalent volume.

Results: Computed cellular S-values S(N→N) for Iodine-125 agree within 1.3% of both MIRDCELL and other Monte Carlo calculations found in literature and S(N→N) values for Bromine-77 agree within 22% of MIRDCELL values, likely attributable to differences in physics definitions for low energy auger emissions.

Conclusion: Initial steps have been taken to develop a microdosimetry platform capable of elucidating microdosimetric properties of targeted radionuclide therapy agents at the sub-cellular level. Simulations performed demonstrate the importance of utilizing realistic and accurate simulation parameters such as realistic cellular geometries captured from Z-stacked confocal microscopy instead of simple spherical volumes. Future work will investigate the dosimetric impact of additional isotopes at the cellular level.

Author Disclosure: D. Adam: None. N. Schweitzer: None. S. Hoffman: None. B. Bednarz: Partnership; Voximetry, LLC.

David Adam, MS

University of Wisconsin-Madison

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