Room: AAPM ePoster Library
Purpose: Radiopharmaceutical therapy is experiencing a renaissance, with several isotopes and targeted delivery systems being used clinically or are currently under investigation. Dosimetry at the cellular level is complex due to inhomogeneity and incomplete targeting of cells in tumors. Unlike external beam modalities, the biological impact of microdosimetric heterogeneity is poorly understood both in vitro and in vivo. Microdosimetric quantities should be considered when evaluating radiopharmaceuticals against other radiotherapy modalities to best inform treatment planning decisions. To this end, this work compares microdosimetric quantities between an xRad320 cabinet irradiator, a 6MV Varian TrueBeam, and radioisotopes I-131, Lu-177, and Ra-223 using Monte Carlo track structure simulations.
Methods: A multi-scale approach was used in GEANT4 to generate the external beam electron spectra and to perform the microscopic track structure simulations. First, electron energy and momentum spectrum in a phantom typical of each radiotherapy modalities’ specific irradiation conditions were calculated. Next, an accompanying GEANT4-DNA track structure simulation was then executed to score the specific and lineal energy for the radioisotopes and external beam sources to spheres of radii 0.1 to 10 microns.
Results: The dose mean lineal energy of Ra-223 is the largest for all sphere sizes considered, while the 6MV TrueBeam is smallest. The recorded momentum spectra from the electron generation simulations indicate isotropic emission does not accurately characterize external beam modalities and thus electron momentum distributions were incorporated into the track structure simulations. The lineal energy distributions and resultant mean lineal energy are sensitive to cell sizes and decrease as the sphere size increases.
Conclusion: Microdosimetric differences are present between all irradiation conditions tested. These differences can impact the results of radiobiological studies and should be carefully considered. Furthermore, the characterization of microdosimetric quantities associated with radiopharmaceutical therapy procedures can better inform treatment planning decisions and potentially improve patient outcomes.
Funding Support, Disclosures, and Conflict of Interest: This work is supported by NIH U01CA233102-01. BB and JG are co-founders of Voximetry, Inc., a nuclear medicine dosimetry company in Madison, WI.