|
|
树脂与玻璃钇90微球在肝细胞癌治疗中的比较：疗效、安全性与技术考量
|
Abstract:
肝细胞癌(HCC)是全球高发的恶性肿瘤，多数患者确诊时已处于中晚期，亟需更有效的局部治疗手段。选择性内放射治疗(SIRT)通过肝动脉输送载有钇-90 (Y-90)的微球，实现对肿瘤的高剂量内照射。目前临床广泛应用的两类微球——树脂微球(SIR-Spheres)与玻璃微球(TheraSphere)，在物理特性、剂量分布、技术工艺及临床疗效上存在显著差异。本文系统比较了两种微球在HCC治疗中的疗效、安全性及技术考量。物理特性方面，树脂微球多孔、密度较低，处方活性较低；玻璃微球结构致密、比活度高，可实现更高的肿瘤吸收剂量。临床疗效方面，两者在客观缓解率与疾病控制率上总体可比，但在特定亚组中存在分化：大肿瘤(≥5 cm)患者可能更受益于树脂微球，而合并门静脉癌栓者使用玻璃微球显示出更长的总生存期和更低毒性。安全性方面，树脂微球术后栓塞综合征更常见，放射性肝损伤风险与非肿瘤肝组织剂量相关；玻璃微球因沉积更稳定，非靶向播散风险较低。剂量学研究表明，分区模型较传统体表面积法具有更优的生存预测效能，且术前99mTc-MAA显像与实际微球分布存在偏差，需结合术后成像验证。针对特殊人群，门静脉癌栓与大肿瘤患者需个体化选择微球类型与剂量策略。当前研究仍面临微球异质性影响临床试验可比性、成本效益分析缺失等问题。未来应推动生物标志物指导的精准选择及人工智能辅助剂量优化。综上，树脂与玻璃Y-90微球在HCC治疗中各有优势，临床决策应基于肿瘤负荷、肝功能、门静脉状态及治疗目标，通过多学科团队协作实现个体化治疗。
Hepatocellular Carcinoma (HCC) is a highly prevalent malignancy worldwide, with most patients diagnosed at intermediate to advanced stages, underscoring the urgent need for more effective locoregional therapies. Selective Internal Radiation Therapy (SIRT) delivers Yttrium-90 (Y-90)-loaded microspheres via the hepatic artery, enabling high-dose internal irradiation of tumors. The two clinically available microsphere types—resin (SIR-Spheres) and glass (TheraSphere)—exhibit substantial differences in physical properties, dosimetric distribution, manufacturing techniques, and clinical outcomes. This review systematically compares the efficacy, safety, and technical considerations of resin versus glass Y-90 microspheres in HCC treatment. Regarding physical characteristics, resin microspheres are porous with lower density and prescribed activity, whereas glass microspheres possess a dense structure, higher specific activity, and achieve greater tumor-absorbed doses. In terms of clinical efficacy, objective response rates and disease control rates are generally comparable; however, subgroup analyses reveal differential outcomes: resin microspheres may confer superior survival benefits in patients with large tumors (≥5 cm), while glass microspheres demonstrate prolonged overall survival and reduced toxicity in those with portal vein tumor thrombosis. Safety profiles differ, with resin microspheres associated with a higher incidence of post-embolization syndrome and radiation-induced liver disease correlated with non-tumoral liver dose; glass microspheres exhibit more stable deposition and lower risk of non-target embolization. Dosimetric evidence supports the superiority of partition model over traditional body surface area
| [1] | Mantry, P.S., Mehta, A., Madani, B., Mejia, A. and Shahin, I. (2017) Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres in Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Study. Journal of Gastrointestinal Oncology, 8, 799-807. https://doi.org/10.21037/jgo.2017.08.03 |
| [2] | Vilgrain, V., Pereira, H., Assenat, E., Guiu, B., Ilonca, A.D., Pageaux, G., et al. (2017) Efficacy and Safety of Selective Internal Radiotherapy with Yttrium-90 Resin Microspheres Compared with Sorafenib in Locally Advanced and Inoperable Hepatocellular Carcinoma (SARAH): An Open-Label Randomised Controlled Phase 3 Trial. The Lancet Oncology, 18, 1624-1636. https://doi.org/10.1016/s1470-2045(17)30683-6 |
| [3] | Li, Z., Xie, C. and Cai, H. (2025) Overview of Yttrium-90 Radioembolization for Advanced Hepatocellular Carcinoma: Current Status and Future Perspectives. World Journal of Clinical Oncology, 16, Article ID: 109730. https://doi.org/10.5306/wjco.v16.i9.109730 |
| [4] | Liu, D.M., Leung, T.W., Chow, P.K., Ng, D.C., Lee, R., Kim, Y.H., et al. (2022) Clinical Consensus Statement: Selective Internal Radiation Therapy with Yttrium 90 Resin Microspheres for Hepatocellular Carcinoma in Asia. International Journal of Surgery, 102, Article ID: 106094. https://doi.org/10.1016/j.ijsu.2021.106094 |
| [5] | Affonso, B.B., Motta-Leal-Filho, J.M.d., Cavalcante Jr., F.d.A., Galastri, F.L., Cavalcante, R.N., Falsarella, P.M., et al. (2017) Aspects of Images in Magnetic Resonance of Liver Tumors Treated with Transarterial Selective Internal Radiotherapy with Yttrium-90. Einstein (São Paulo), 16, eRC4015. https://doi.org/10.1590/s1679-45082017rc4015 |
| [6] | Westcott, M.A., Coldwell, D.M., Liu, D.M. and Zikria, J.F. (2016) The Development, Commercialization, and Clinical Context of Yttrium-90 Radiolabeled Resin and Glass Microspheres. Advances in Radiation Oncology, 1, 351-364. https://doi.org/10.1016/j.adro.2016.08.003 |
| [7] | Shah, R.M., Sheikh, S., Shah, J., Vivian, E., Mejia, A., Shahin, I., et al. (2021) Prognostic Factors of Unresectable Hepatocellular Carcinoma Treated with Yttrium-90 Radioembolization: Results from a Large Cohort over 13 Years at a Single Center. Journal of Gastrointestinal Oncology, 12, 1718-1731. https://doi.org/10.21037/jgo-20-435 |
| [8] | Sarwar, A., Malik, M.S., Vo, N.H., Tsai, L.L., Tahir, M.M., Curry, M.P., et al. (2024) Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma. Radiology, 311, e231386. https://doi.org/10.1148/radiol.231386 |
| [9] | Chen, K., Tong, A.K.T., Moe, F.N.N., Ng, D.C.E., Lo, R.H.G., Gogna, A., et al. (2024) The Impact of Radiation Dose and Tumour Burden on Outcomes in Hepatocellular Carcinoma: 11-Year Experience in a 413-Patient Cohort Treated with Yttrium-90 Resin Microsphere Radioembolisation. Liver Cancer, 14, 158-179. https://doi.org/10.1159/000541539 |
| [10] | Garin, E., Tselikas, L., Guiu, B., Chalaye, J., Edeline, J., de Baere, T., et al. (2021) Personalised versus Standard Dosimetry Approach of Selective Internal Radiation Therapy in Patients with Locally Advanced Hepatocellular Carcinoma (DOSISPHERE-01): A Randomised, Multicentre, Open-Label Phase 2 Trial. The Lancet Gastroenterology & Hepatology, 6, 17-29. https://doi.org/10.1016/s2468-1253(20)30290-9 |
| [11] | Hang, Z., Hu, H., Liang, Z., Zhang, Y., Yan, C., Zhang, T., et al. (2026) Dosimetric Development of Yttrium‐90 Resin Microspheres for Selective Internal Radiation Therapy: Current Status and Perspectives. Journal of Labelled Compounds and Radiopharmaceuticals, 69, e70022. https://doi.org/10.1002/jlcr.70022 |
| [12] | James, T., Hill, J., Fahrbach, T. and Collins, Z. (2017) Differences in Radiation Activity between Glass and Resin 90Y Microspheres in Treating Unresectable Hepatic Cancer. Health Physics, 112, 300-304. https://doi.org/10.1097/hp.0000000000000631 |
| [13] | Biederman, D.M., Titano, J.J., Tabori, N.E., Pierobon, E.S., Alshebeeb, K., Schwartz, M., et al. (2016) Outcomes of Radioembolization in the Treatment of Hepatocellular Carcinoma with Portal Vein Invasion: Resin versus Glass Microspheres. Journal of Vascular and Interventional Radiology, 27, 812-821.e2. https://doi.org/10.1016/j.jvir.2016.01.147 |
| [14] | Zheng, X., Xi, H., Kater, G.M., Bloemsma, G.C., Bokkers, R.P.H., Mazuri, A., et al. (2025) Single-Center Experience Comparing Glass and Resin Microspheres in Lobar Y-90 SIRT for Early-to Intermediate-Stage Hepatocellular Carcinoma. EJNMMI Research, 15, Article No. 145. https://doi.org/10.1186/s13550-025-01343-2 |
| [15] | Kim, G.M., Kim, D.Y., Won, J.Y., Moon, S., Kim, S.U. and Kim, B.K. (2024) Outcome of Transarterial Radioembolization in the Treatment of Hepatocellular Carcinoma: Glass versus Resin Microsphere. CardioVascular and Interventional Radiology, 47, 1210-1221. https://doi.org/10.1007/s00270-024-03726-9 |
| [16] | Braat, M.N., Braat, A.J. and Lam, M.G. (2024) Toxicity Comparison of Yttrium-90 Resin and Glass Microspheres Radioembolization. The Quarterly Journal of Nuclear Medicine and Molecular Imaging, 68, 133-142. https://doi.org/10.23736/s1824-4785.22.03452-5 |
| [17] | Noipinit, N., Sukprakun, C., Siricharoen, P. and Khamwan, K. (2024) Comparison of Absorbed Doses to the Tumoral and Non-Tumoral Liver in HCC Patients Undergoing 99mtc-Maa and 90Y-Microspheres Radioembolization. Annals of Nuclear Medicine, 38, 210-218. https://doi.org/10.1007/s12149-023-01890-5 |
| [18] | Zhang, H., Pan, X., Wu, Q., Wu, Y., Zheng, N., Ning, S., et al. (2025) Synthesis and Characterization of Functional Chitosan-Based Microspheres as Biodegradable Yttrium-90 Delivery System for Radioembolization Therapy. International Journal of Biological Macromolecules, 312, Article ID: 144090. https://doi.org/10.1016/j.ijbiomac.2025.144090 |
| [19] | Subramanian, S., Pandey, U., Chaudhari, P., Tyagi, M., Gupta, S., Singh, G., et al. (2016) Preliminary Evaluation of Indigenous 90Y-Labelled Microspheres for Therapy of Hepatocellular Carcinoma. Indian Journal of Medical Research, 143, S74-S81. https://doi.org/10.4103/0971-5916.191786 |
| [20] | Garin, E., Guiu, B., Edeline, J., Rolland, Y. and Palard, X. (2022) Trans-Arterial Radioembolization Dosimetry in 2022. CardioVascular and Interventional Radiology, 45, 1608-1621. https://doi.org/10.1007/s00270-022-03215-x |
| [21] | Vimalnath, K.V., Rajeswari, A., Dixit, A., Chakravarty, R., Sarma, H.D., Kulkarni, S., et al. (2024) [90Y]yttria Alumino Silicate Glass Microspheres: A Biosimilar Formulation to “TheraSphere” for Cost-Effective Treatment of Liver Cancer. Cancer Biotherapy and Radiopharmaceuticals, 39, 82-91. https://doi.org/10.1089/cbr.2023.0118 |
| [22] | Nezami, N., Kokabi, N., Camacho, J.C., Schuster, D.M., Xing, M. and Kim, H.S. (2018) 90Y Radioembolization Dosimetry Using a Simple Semi-Quantitative Method in Intrahepatic Cholangiocarcinoma: Glass versus Resin Microspheres. Nuclear Medicine and Biology, 59, 22-28. https://doi.org/10.1016/j.nucmedbio.2018.01.001 |
| [23] | Kim, H., Kim, Y.J., Lee, J., Suh, K. and Chung, J.W. (2019) Feasibility of Boosted Radioembolization for Hepatocellular Carcinoma Larger than 5 cm. Journal of Vascular and Interventional Radiology, 30, 1-8. https://doi.org/10.1016/j.jvir.2018.07.002 |
| [24] | Feely, M., Tondon, R., Gubbiotti, M., Stashek, K.M., Numbere, N., Huber, A.R., et al. (2022) Gastrointestinal Tract Injury by Yttrium-90 Appears Largely Restricted to Resin Microspheres but Can Occur Years after Embolization. American Journal of Surgical Pathology, 46, 1234-1240. https://doi.org/10.1097/pas.0000000000001901 |
| [25] | Miller, S.R., Jernigan, S.R., Abraham, R.J. and Buckner, G.D. (2023) Comparison of Bolus versus Dual-Syringe Administration Systems on Glass Yttrium-90 Microsphere Deposition in an in Vitro Microvascular Hepatic Tumor Model. Journal of Vascular and Interventional Radiology, 34, 11-20. https://doi.org/10.1016/j.jvir.2022.07.032 |
| [26] | Soydaş-Turan, B., Bozkurt, M.F., Eldem, G., Peynircioglu, B., Ugur, O. and Volkan-Salanci, B. (2025) Comparing Laboratory Toxicity of Selective Intra-Arterial Radionuclide Therapy for Primary and Metastatic Liver Tumors: Resin versus Glass Microspheres. Annals of Nuclear Medicine, 39, 373-379. https://doi.org/10.1007/s12149-024-02011-6 |
| [27] | Yu, C., Huang, P., Tsang, L.L., Hsu, H., Lim, W., Weng, C., et al. (2023) Yttrium-90 Radioembolization as the Major Treatment of Hepatocellular Carcinoma. Journal of Hepatocellular Carcinoma, 10, 17-26. https://doi.org/10.2147/jhc.s385478 |
| [28] | Kolligs, F., Arnold, D., Golfieri, R., Pech, M., Peynircioglu, B., Pfammatter, T., et al. (2023) Factors Impacting Survival after Transarterial Radioembolization in Patients with Hepatocellular Carcinoma: Results from the Prospective CIRT Study. JHEP Reports, 5, Article ID: 100633. https://doi.org/10.1016/j.jhepr.2022.100633 |
| [29] | Kim, H., Lee, M., Lee, J., Paeng, J.C., Kim, Y.J. and Chung, J.W. (2020) Combination of 1st and 2nd Week Dosing of Glass Yttrium-90 Microspheres for Superselective Radioembolization. In Vivo, 34, 2763-2768. https://doi.org/10.21873/invivo.12100 |
| [30] | Cardarelli-Leite, L., Chung, J., Klass, D., Marquez, V., Chou, F., Ho, S., et al. (2020) Ablative Transarterial Radioembolization Improves Survival in Patients with HCC and Portal Vein Tumor Thrombus. CardioVascular and Interventional Radiology, 43, 411-422. https://doi.org/10.1007/s00270-019-02404-5 |
| [31] | Srinivas, S.M., Nasr, E.C., Kunam, V.K., Bullen, J.A. and Purysko, A.S. (2016) Administered Activity and Outcomes of Glass versus Resin 90Y Microsphere Radioembolization in Patients with Colorectal Liver Metastases. Journal of Gastrointestinal Oncology, 7, 530-539. https://doi.org/10.21037/jgo.2016.03.09 |
| [32] | Brown, D., Krebs, H., Brower, J., O’Hara, R., Wang, E., Vaheesan, K., et al. (2021) Incidence and Risk Factors for Sustained Hepatic Function Toxicity 6 Months after Radioembolization: Analysis of the Radiation-Emitting Sir-Spheres in Non-Resectable Liver Tumor (RESIN) Registry. Journal of Gastrointestinal Oncology, 12, 639-657. https://doi.org/10.21037/jgo-20-346 |
| [33] | Chan, L.S., Sze, D.Y., Poultsides, G.A., Louie, J.D., Abdelrazek Mohammed, M.A. and Wang, D.S. (2017) Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma. CardioVascular and Interventional Radiology, 40, 1383-1391. https://doi.org/10.1007/s00270-017-1648-7 |
| [34] | Busse, N.C., Al‐Ghazi, M.S.A.L., Abi‐Jaoudeh, N., Alvarez, D., Ayan, A.S., Chen, E., et al. (2024) AAPM Medical Physics Practice Guideline 14.a: Yttrium‐90 Microsphere Radioembolization. Journal of Applied Clinical Medical Physics, 25, e14157. https://doi.org/10.1002/acm2.14157 |
| [35] | Wallace, M.C., Samuelson, S., Khoo, T., Ooi, J., Tibballs, J., Ferguson, J., et al. (2020) The MAAPE Score in Intermediate and Advanced Hepatocellular Carcinoma Treated with Yttrium‐90 Resin Microsphere Radioembolization. Journal of Gastroenterology and Hepatology, 35, 1945-1952. https://doi.org/10.1111/jgh.15008 |
| [36] | Gallio, E., Richetta, E., Finessi, M., Stasi, M., Pellerito, R.E., Bisi, G., et al. (2016) Calculation of Tumour and Normal Tissue Biological Effective Dose in 90Y Liver Radioembolization with Different Dosimetric Methods. Physica Medica, 32, 1738-1744. https://doi.org/10.1016/j.ejmp.2016.10.023 |
| [37] | Bastiaannet, R., Kappadath, S.C., Kunnen, B., Braat, A.J.A.T., Lam, M.G.E.H. and de Jong, H.W.A.M. (2018) The Physics of Radioembolization. EJNMMI Physics, 5, Article No. 22. https://doi.org/10.1186/s40658-018-0221-z |
| [38] | Qin, X., Jia, Z., Jiang, G., Tian, F. and Zhu, C. (2016) A Systematic Review on the Safety and Effectiveness of Yttrium-90 Radioembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis. Saudi Journal of Gastroenterology, 22, 353-359. https://doi.org/10.4103/1319-3767.191139 |
| [39] | Cho, Y.Y., Lee, M., Kim, H., Chung, J.W., Kim, Y.H., Gwak, G., et al. (2016) Radioembolization Is a Safe and Effective Treatment for Hepatocellular Carcinoma with Portal Vein Thrombosis: A Propensity Score Analysis. PLOS ONE, 11, e0154986. https://doi.org/10.1371/journal.pone.0154986 |
| [40] | Choi, J.W., Suh, M., Choi, Y., Lee, M., Paeng, J.C. and Kim, H.C. (2026) Yttrium-90 Glass Microsphere Radioembolization as Frontline Treatment for Hepatocellular Carcinoma with Localized Portal Vein Invasion. European Radiology, 36, 743-753. https://doi.org/10.1007/s00330-025-11882-w |
| [41] | Lam, M., Garin, E., Maccauro, M., Kappadath, S.C., Sze, D.Y., Turkmen, C., et al. (2022) A Global Evaluation of Advanced Dosimetry in Transarterial Radioembolization of Hepatocellular Carcinoma with Yttrium-90: The TARGET Study. European Journal of Nuclear Medicine and Molecular Imaging, 49, 3340-3352. https://doi.org/10.1007/s00259-022-05774-0 |
| [42] | Subreville, C., Pinaquy, J., Lapuyade, B., Blanc, J., Bordenave, L., Papadopoulos, P., et al. (2021) Key Role of Personalized Dosimetry in Dose Adjustment for Selective Internal Radiotherapy: Retrospective Study of Patients Treated with 90Y Resin Microspheres. Clinical Nuclear Medicine, 46, 958-964. https://doi.org/10.1097/rlu.0000000000003892 |
| [43] | Jha, A.K., Puranik, A.D., Gala, K.B., Nair, K.V.V., Rajeswari, A., Lohar, S.P., et al. (2025) First-in-India Experience with 90y-Bhabhasphere: An Indigenous 90y-Therasphere Biosimilar for Transarterial Radioembolization of Hepatic Malignancies. British Journal of Radiology, 98, 2135-2143. https://doi.org/10.1093/bjr/tqaf197 |
| [44] | Ho, C.L., Chen, S., Cheung, S.K., Leung, Y.L., Cheng, K.C., Wong, K.N., et al. (2018) Radioembolization with 90Y Glass Microspheres for Hepatocellular Carcinoma: Significance of Pretreatment 11c-Acetate and 18F-FDG PET/CT and Posttreatment 90Y PET/CT in Individualized Dose Prescription. European Journal of Nuclear Medicine and Molecular Imaging, 45, 2110-2121. https://doi.org/10.1007/s00259-018-4064-6 |
| [45] | Borgheresi, R., Barucci, A., Colantonio, S., Aghakhanyan, G., Assante, M., Bertelli, E., et al. (2022) NAVIGATOR: An Italian Regional Imaging Biobank to Promote Precision Medicine for Oncologic Patients. European Radiology Experimental, 6, Article No. 53. https://doi.org/10.1186/s41747-022-00306-9 |
| [46] | Boas, F.E., Bodei, L. and Sofocleous, C.T. (2017) Radioembolization of Colorectal Liver Metastases: Indications, Technique, and Outcomes. Journal of Nuclear Medicine, 58, 104S-111S. https://doi.org/10.2967/jnumed.116.187229 |
| [47] | d’Abadie, P., Walrand, S., Hesse, M., Annet, L., Borbath, I., Van den Eynde, M., et al. (2021) Prediction of Tumor Response and Patient Outcome after Radioembolization of Hepatocellular Carcinoma Using 90Y-PET-Computed Tomography Dosimetry. Nuclear Medicine Communications, 42, 747-754. https://doi.org/10.1097/mnm.0000000000001395 |
| [48] | Kallini, J.R., Gabr, A., Thorlund, K., Balijepalli, C., Ayres, D., Kanters, S., et al. (2017) Comparison of the Adverse Event Profile of Therasphere® with Sir-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review. CardioVascular and Interventional Radiology, 40, 1033-1043. https://doi.org/10.1007/s00270-017-1594-4 |
| [49] | Gao, X., Zhang, M., Fang, D., Yu, Y., Qi, S., Yu, X., et al. (2025) Mineralization of Macroaggregated Albumin for Accurate Biodistribution Evaluation of Pre-Radiotherapy. Chemical Communications, 61, 7313-7316. https://doi.org/10.1039/d5cc01204j |
| [50] | Auditore, L., Pistone, D., Italiano, A., Amato, E. and Gnesin, S. (2023) Monte Carlo Simulations Corroborate Pet-Measured Discrepancies in Activity Assessments of Commercial 90Y Vials. Journal of Nuclear Medicine, 64, 1471-1477. https://doi.org/10.2967/jnumed.123.265494 |
| [51] | Filippi, L., Evangelista, L. and Schillaci, O. (2023) Integrated Use of 90Y-Labeled Microspheres and Immune Checkpoint Inhibitors in Hepatic Tumors: Current Status and Future Directions. Expert Review of Gastroenterology & Hepatology, 17, 531-538. https://doi.org/10.1080/17474124.2023.2215981 |
