Iodine-131 radioembolization boosts the immune activation enhanced by icaritin/resiquimod in hepatocellular carcinoma

Xinyi Li; Yuyi Qian; Xin Lu; Mingzhen Xu; Simin He; Jianping Zhang; Shaoli Song

doi:10.1016/j.jconrel.2024.12.064

Iodine-131 radioembolization boosts the immune activation enhanced by icaritin/resiquimod in hepatocellular carcinoma

J Control Release. 2024 Dec 25:S0168-3659(24)00919-2. doi: 10.1016/j.jconrel.2024.12.064. Online ahead of print.

Authors

Xinyi Li¹, Yuyi Qian¹, Xin Lu¹, Mingzhen Xu¹, Simin He¹, Jianping Zhang¹, Shaoli Song²

Affiliations

¹ Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China.
² Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China; Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai 200433, China. Electronic address: [email protected].

PMID: 39730069
DOI: 10.1016/j.jconrel.2024.12.064

Abstract

Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) ¹³¹I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 (¹³¹I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation. Decellularized liver model and SPECT/CT imaging revealed high specificity and long retention of microspheres. Radioactive distribution of ¹³¹I in tumor on 7 d following ¹³¹I-MS injection was over 7 times of that in normal liver tissue (4.26 ± 1.21 % ID/g vs 0.57 ± 0.23 % ID/g). ¹³¹I-ICT/R848-MS embolization brought significant immune activation, where the ratio of cytotoxic T lymphocytes to regulatory T cells in tumor sites upregulated from 1.75 ± 0.20 to 24.31 ± 1.79, and DC maturation in lymph nodes increased from 8.90 ± 1.51 % to 34.70 ± 3.12 %. Enhanced anti-tumor efficacy with no relapse was proved in rat orthotopic N1S1 HCC models. These results demonstrated the great potential of this multifunctional embolic agent to treat HCC through transarterial radio-immuno-chemoembolization (TARICE).

Keywords: Combination therapy; Hepatocellular carcinoma; Immune adjuvant; Immunogenic cell death; Radionuclide therapy; Transarterial radioembolization.