Post-therapeutic dosimetric evaluation of ¹⁶⁶Ho radioembolization for liver malignancies: Impact of software on tumor and liver doses

Abstract

Transarterial radioembolization using holmium-166 microspheres is a promising treatment for primary and secondary liver malignancies. Accurate post-therapeutic dosimetry is critical for optimizing outcomes, particularly in voxel-based dose assessment using quantitative single-photon emission computed tomography/computed tomography (SPECT/CT). This study aimed to evaluate the impact of software choice and calibration method on absorbed dose estimates to the liver and tumor, by comparing two advanced dosimetry platforms: Hermia Voxel Dosimetry^TM and Q-Suite^TM. Despite the recent discontinuation of ¹⁶⁶Ho-microsphere production, such studies remain highly relevant given the global emphasis on personalized dosimetry, quantitative imaging in nuclear medicine, and potential applicability to other therapeutic radiopharmaceuticals and future microsphere technologies. Fourteen patients underwent a scout procedure, followed by therapy and post-treatment SPECT/CT imaging. Initial analysis revealed substantially lower mean liver and tumor doses with Hermia (12 ± 4 Gy and 58 ± 23 Gy) compared to Q-Suite (44 ± 9 Gy and 209 ± 83 Gy), with statistically significant differences (p=0.002 and p<0.001). Discrepancies were due to the gamma camera dead time and Hermia’s fixed calibration factor (CF). A patient-specific CF, derived from the camera’s response curve and administered activity, was applied to correct Hermia dose maps. The corrected doses, 42 ± 6 Gy and 196 ± 17 Gy, closely matched those from Q-Suite (p=0.69 and p=0.64). These findings underscore the critical role of system-specific calibration and acquisition timing in achieving accurate voxel-based dosimetry. Underestimation of absorbed doses may lead to suboptimal clinical decisions, including undertreatment or unrecognized toxicity. Thus, implementing patient-specific calibration protocols or equivalent corrections for dead time is essential to support safe, consistent, and effective radionuclide therapy in clinical practice.

Keywords

Calibration factor / Gamma camera response / Holmium-166 / Transarterial radioembolization / Personalized radionuclide therapy / Single-photon emission computed tomography/computed tomography quantification / Voxel-based dosimetry

References

[1] Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022; 77:1598-1606. doi: 10.1016/j.jhep.2022.08.021

[2] Wang ZG, He ZY, Chen YY, Gao H, Du XL. Incidence and survival outcomes of secondary liver cancer: A Surveillance Epidemiology and End Results database analysis. Transl Cancer Res. 2021; 10(3):1273-1283. doi: 10.21037/tcr-20-3319

[3] Sólymos P, Rédei M, Turan C, et al. Holmium-166 radioembolization is a safe and effective locoregional treatment for primary and secondary liver tumors: A systematic review and meta-analysis. Cancers (Basel). 2025; 17(11):1841. doi: 10.3390/cancers17111841

[4] Reinders MTM, Smits MLJ, Roekel C, Braat AJAT. Holmium-166 microsphere radioembolization of hepatic malignancies. Semin Nuclear Med. 2019; 49(3):237-243. doi: 10.1053/j.semnuclmed.2019.01.008

[5] Stella M, Braat AJAT, Lam MGEH, Jong HWAM, Rooij R. Gamma camera characterization at high holmium-166 activity in liver radioembolization. EJNMMI Phys. 2021; 8(1):22. doi: 10.1186/s40658-021-00372-9

[6] Stella M, Braat AJAT, Rooij R, Jong HWAM, Lam MGEH. Holmium-166 radioembolization: Current status and future prospective. Cardiovasc Intervent Radiol. 2022; 45(11):1634-1645. doi: 10.1007/s00270-022-03187-y

[7] Drescher R, Seifert P, Gühne F, et al. Radioembolization with holmium-166 polylactic acid microspheres: Distribution of residual activity in the delivery set and outflow dynamics during planning and treatment procedures. J Endovas Ther. 2021; 28(3):452-462. doi: 10.1177/1526602821996719

[8] Smits MLJ, Elschot M, van den Bosch MA et al. In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for treatment of liver malignancies. J Nucl Med. 2013; 54(12):2093-2100. doi: 10.2967/jnumed.113.119768

[9] Hobbs RF, Baechler S, Senthamizhchelvan S, et al. A gamma camera count rate saturation correction method for whole-body planar imaging. Phys Med Biol. 2010; 55(3):817-831. doi: 10.1088/0031-9155/55/3/018

[10] Danieli R, Milano A, Gallo S, et al. Personalized dosimetry in targeted radiation therapy: A look to methods, tools and critical aspects. J Pers Med. 2022; 12(2):205. doi: 10.3390/jpm12020205

[11] Cassano B, Miseo L, Ungania S, et al. Dosimetric study on radioembolization with 166Ho poly L-lactic acid microspheres: Dead time effects on prediction power. EJNMMI Phys. 2025; 12:64. doi: 10.1186/s40658-025-00779-8

[12] Sjögreen-Gleisner K, Flux G, Bacher K, et al. EFOMP policy statement NO. 19: Dosimetry in nuclear medicine therapy - Molecular radiotherapy. Phys Med. 2023; 116:103166. doi: 10.1016/j.ejmp.2023.103166

[13] Reinders MTM, Braat AJAT, van Erpecum KJ, et al. Holmium-166 radioembolisation dosimetry in HCC. Eur J Nucl Med Mol Imaging. 2025; 52:993-1003. doi: 10.1007/s00259-024-06940-2

[14] Ramonaheng K, du Raan H. The effect of calibration factors and recovery coefficients on 177Lu SPECT activity quantification accuracy: A Monte Carlo study. EJNMMI Phys. 2021; 8(1):27. doi: 10.1186/s40658-021-00365-8

[15] Elschot M.Quantitative Nuclear Imaging for Dosimetry in Radioembolization. Dissertation. Utrecht University; 2013.

[16] Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022; 76(3):681-693. doi: 10.1016/j.jhep.2021.11.018

[17] Drescher R, Köhler A, Seifert P, et al. Clinical results of transarterial radioembolization (TARE) with holmium-166 microspheres in the multidisciplinary oncologic treatment of patients with primary and secondary liver cancer. Biomedicines. 202326;11(7): 1831. doi: 10.3390/biomedicines11071831

[18] Dickson JC, Armstrong IS, Gabiña PM et al. EANM practice guideline for quantitative SPECT-CT. Eur J Nucl Med Mol Imaging. 202350(4):980-995. doi: 10.1007/s00259-022-06028-9

[19] Hippeläinen ET, Tenhunen MJ, Mäenpää HO, Heikkonen JJ, Sohlberg AO. Dosimetry software Hermes Internal Radiation Dosimetry: From quantitative image reconstruction to voxel-level absorbed dose distribution. Nucl Med Commun. 2017; 38(5):357-365. doi: 10.1097/MNM.0000000000000662

[20] Hippeläinen E, Tenhunen M, Sohlberg A. Fast voxel-level dosimetry for 177Lu labelled peptide treatments. Phys Med Biol. 2015; 60(17):6685-6700. doi: 10.1088/0031-9155/60/17/6685

[21] Kästner D, Braune A, Brogsitter C, et al. Gamma camera imaging characteristics of 166Ho and 99mTc used in Selective Internal Radiation Therapy. EJNMMI Phys. 2024; 11:35. doi: 10.1186/s40658-024-00633-3