Yttrium-90 ( ) represents the primary radioisotope used in radioembolization procedures, while holmium-166 ( ) is hypothesized to serve as a viable substitute for due to its comparable therapeutic potential and improved quantitative imaging. Voxel-based dosimetry for these radioisotopes relies on activity images obtained through PET or SPECT and dosimetry methods, including the voxel S-value (VSV) and the local deposition method (LDM). However, the evaluation of the accuracy of absorbed dose calculations has been limited by the use of non-ideal reference standards and investigations restricted to the liver. The objective of this study was to expand upon these dosimetry characterizations by investigating the impact of image resolutions, voxel sizes, target volumes, and tissue materials on the accuracy of and dosimetry techniques. A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated kernels with published data. The decay spectra of both and were also compared. Multiple VSV kernels were generated for the liver, lungs, soft tissue, and bone for isotropic voxel sizes of 1 mm, 2 mm, and 4 mm. Three theoretical phantom setups were created with 20 or 40mm activity and mass density inserts for the same three voxel sizes. To replicate the limited spatial resolutions present in PET and SPECT images, image resolutions were modeled using a 3D Gaussian kernel with a Full Width at Half Maximum (FWHM) ranging from 0 to 16mm and with no added noise. The VSV and LDM dosimetry methods were evaluated by characterizing their respective kernels and analyzing their absorbed dose estimates calculated on theoretical phantoms. The ground truth for these estimations was calculated usingreDoseMC. The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9MeV in the case of and less than 1% for energies below 1.5MeV for . Additionally, the validation kernels for VSV exhibited results similar to those found in published Monte Carlo codes, with source dose depositions having less than a 3% error margin. Resolution thresholds ( ), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for . They were 1.5mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For , the accuracy of absorbed dose deposition was found to be dependent on the contributions of absorbed dose from photons. Volume errors due to variations in voxel size impacted the final dose estimates. Larger target volumes yielded more accurate mean doses than smaller volumes. For both radioisotopes, the radial dose profiles for the VSV and LDM approximated but never matched the referencestandard. reDoseMC was developed and validated for radiopharmaceutical dosimetry. The accuracy of voxel-based dosimetry was found to vary widely with changes in image resolutions, voxel sizes, chosen target volumes, and tissue material; hence, the standardization of dosimetry protocols was found to be of great importance for comparable dosimetryanalysis.
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