Characterizing the voxel-based approaches in radioembolization dosimetry with reDoseMC.

BACKGROUND: Yttrium-90 ( 90 Y $^{90}{\rm {Y}}$ ) represents the primary radioisotope used in radioembolization procedures, while holmium-166 ( 166 Ho $^{166}{\rm {Ho}}$ ) is hypothesized to serve as a viable substitute for 90 Y $^{90}{\rm {Y}}$ 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 90 Y $^{90}{\rm {Y}}$ and 166 Ho $^{166}{\rm {Ho}}$ dosimetry techniques. METHODS: A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated 90 Y $^{90}{\rm {Y}}$ kernels with published data. The decay spectra of both 90 Y $^{90}{\rm {Y}}$ and 166 Ho $^{166}{\rm {Ho}}$ 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 40 mm 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 16 mm 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 using reDoseMC. RESULTS: The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9 MeV in the case of 90 Y $^{90}{\rm {Y}}$ and less than 1% for energies below 1.5 MeV for 166 Ho $^{166}{\rm {Ho}}$ . Additionally, the validation kernels for 90 Y $^{90}{\rm {Y}}$ 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 ( FWHM thresh s ${\rm {FWHM}}_\mathrm{thresh}{\rm {s}}$ ), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for 90 Y $^{90}{\rm {Y}}$ . They were 1.5 mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For 166 Ho $^{166}{\rm {Ho}}$ , 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 reference standard. CONCLUSIONS: 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 dosimetry analysis.

Use of dose-volume histograms for metabolic response prediction in hepatocellular carcinoma patients undergoing transarterial radioembolization with Y-90 resin microspheres.

INTRODUCTION: Voxel-based dosimetry offers improved outcomes in the treatment of hepatocellular carcinoma (HCC) with transarterial radioembolization (TARE) using glass microspheres. However, the adaptation of voxel-based dosimetry to resin-based microspheres has been poorly studied, and the prognostic relevance of heterogeneous dose distribution remains unclear. This study aims to explore the use of dose-volume histograms for resin microspheres and to determine thresholds for objective metabolic response in HCC patients treated with resin-based TARE. METHODS: We retrospectively reviewed HCC patients who underwent TARE with Y-90-loaded resin microspheres in our institution between January 2021 and December 2022. Voxel-based dosimetry was performed on post-treatment Y-90 PET/CT images to extract parameters including mean dose absorbed by the tumor (mTD), the percentage of the targeted tumor volume (pTV), and the minimum doses absorbed by consecutive percentages within the tumor volume (D10, D25, D50, D75, D90). Assessment of metabolic response was done according to PERCIST criteria with F-18 FDG PET/CT imaging at 8-12 weeks after the treatment. RESULTS: This study included 35 lesions targeted with 22 TARE sessions in 19 patients (15 males, 4 females, mean age 60 ± 13 years). Objective metabolic response was achieved in 43% of the lesions (n = 15). Responsive lesions had significantly higher mTD, pTV, and D25-D90 values (all p < 0.05). Optimal cut-off values for mTD, pTV, and D50 were 94.6 Gy (sensitivity 73%, specificity 70%, AUC 0.72), 94% (sensitivity 73%, specificity 55%, AUC 0.64), and 91 Gy (sensitivity 80%, specificity 80%, AUC 0.80), respectively. CONCLUSION: Parameters derived from dose-volume histograms could offer valuable insights for predicting objective metabolic response in HCC patients treated with resin-based TARE. If verified with larger prospective cohorts, these parameters could enhance the precision of dose distribution and potentially optimize treatment outcomes.