Trackable Radioactive ¹⁷⁷Lu-Microspheres Induce Immunogenic Cell Death by Transarterial Radioembolization Therapy in Hepatocellular Carcinoma

Due to lacking real-time feedback of radioembolization microsphere distribution during interventional operation, transarterial radioembolization therapy confronts significant technical challenges to avoid side effects caused by ectopic embolization. This study develops trackable poly(vinyl alcohol) microspheres (DPT MPs) conjugated with 2,3,5-triiodobenzaldehyde for intraprocedural visualization via fluoroscopy or cone-beam computed tomography. Meanwhile, lutecium-177 ( 177 Lu), a theranostic radionuclide, is labeled for brachytherapy and long-term monitoring post embolization by micro -single photon emission computed tomography/computed tomography imaging. 177 Lu-DPT MPs achieve ultrahigh specific activity (0.74 mCi/mg) and maintain radiostability over 28 d. The cumulative absorbed radiation doses of tumor tissue are at least 42-fold higher than that of peritumoral liver tissue, which is attributed to specific tumor targeting and prolonged retention of 177 Lu-DPT MPs. Furthermore, 177 Lu-DPT MPs can observably inhibit tumor growth without notable side effects. These findings indicate that 177 Lu-DPT MPs are promising trackable embolic agents for clinical radioembolization therapy.