Radionuclide Therapy Applications in Hepatocellular Carcinoma

Radionuclide therapy has emerged as a pivotal modality in the management of hepatocellular carcinoma (HCC), particularly for patients who are unsuitable for surgical resection or transplantation. By delivering cytotoxic radiation directly to tumours via the hepatic arterial circulation, therapies such as selective internal radiation therapy (SIRT) and transarterial radioembolization (TARE) maximise dose deposition in malignant tissue while sparing healthy liver parenchyma. Traditionally, yttrium-90-labelled glass or resin microspheres have formed the backbone of TARE protocols, demonstrating improvements in local control and overall survival. In parallel, novel carriers incorporating lutetium-177 and holmium-166 have been developed to combine therapeutic β-emission with γ-emission for real-time imaging and accurate dosimetry. Advances in particle design—from biodegradable polymer composites to phosphonated silica—have enhanced radionuclide loading, biodegradability and biocompatibility. Integration of quantitative imaging modalities (SPECT, PET and MRI) with dosimetric algorithms now allows patient-specific treatment planning and post-treatment assessment. Ongoing research seeks to refine particle size distribution, radionuclide choice and delivery techniques to overcome embolic hypoxia, reduce non-target embolisation and amplify antitumour efficacy. These innovations hold promise for global applicability, offering cost-effective, minimally invasive options for intermediate to advanced HCC across diverse healthcare settings.

Research from Nature Portfolio

Recent clinical investigations have demonstrated the value of integrated dosimetry in optimizing yttrium-90 radioembolization. In a multicentre phase II study, real-time SPECT/CT-guided TARE was shown to improve local tumour control and reduce hepatic toxicity by enabling adjustment of administered activity based on patient-specific vascular distribution. Preclinical work with biodegradable, dual-modality microspheres loaded with lutetium-177 reported precise deposition in orthotopic liver tumours and significantly prolonged survival in animal models; these particles allowed simultaneous PET/MRI tracking and delivered sustained beta-irradiation. Another effort engineered albumin-based nanospheres carrying gradient-release lutetium-177 and demonstrated enhanced uptake in HCC xenografts with minimal off-target accumulation, paving the way for dose-escalation studies in humans.

Radionuclide Therapy Applications in Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in radionuclide therapy applications in hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Radionuclide: An unstable isotope that emits ionising radiation used for both therapeutic and diagnostic purposes.

Selective internal radiation therapy (SIRT): A form of locoregional treatment that delivers radiolabelled particles via the hepatic artery to target liver tumours selectively.

Transarterial radioembolization (TARE): Administration of microspheres loaded with therapeutic radionuclides into tumour-feeding arteries to achieve embolisation and localized irradiation.

Microsphere: A small, often biodegradable, spherical carrier designed to lodge in tumour microvasculature and deliver a radionuclide payload.

Dosimetry: The quantitative measurement and calculation of the absorbed radiation dose in tissues, critical for treatment planning and safety.

References

1. Polymer composite microspheres loading 177Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer. Biomaterials Research (2023).
2. Clinically Translatable Phosphonated Silica Microspheres for Selective Internal Radiation Therapy of Hepatocellular Carcinoma. Small Science (2023).
3. The various therapeutic applications of the medical isotope holmium-166: a narrative review. EJNMMI Radiopharmacy and Chemistry (2019).