The inhibiting effect of alpha-based TARE on embolized vessels and neovascularization

• Published in: Frontiers in bioengineering and biotechnology 2022-10, Vol.10, p.1021499-1021499
• Main Authors: Tong, Qianqian, Li, Rou, Wang, Ruizhi, Zuo, Changjing, Li, Danni, Jia, Guorong, Peng, Ye, Li, Xiaohong, Yang, Jian, Xue, Shuai, Bai, Qingyun, Li, Xiao
• Format: Article
• Language: English
• Subjects: Bioengineering and Biotechnology; hepatocellular carcinoma; neovascularization; Ra-223; silk fibroin; transarterial radioembolization; α radionuclides
• ISSN: 2296-4185; 2296-4185
• DOI: 10.3389/fbioe.2022.1021499

Transarterial embolization (TAE) is a personalized technology that offers precise delivery of chemotherapeutic drugs or selective internal radiation therapy for hepatocellular carcinoma (HCC). Beta-emitting radionuclide embolisms for TAE (β-based TARE) are commonly used in the clinic via inducing biochemical lethality on tumor cells, while alpha-emitting radionuclides-based embolisms for TAE (α-based TARE) are still under study. The feeding artery plays a key role in tumor growth, metastasis, and recurrence. In this research, the auricular central arteries (ACAs) of rabbits were embolized with silk fibroin-based microspheres (SFMs) or SFMs integrated with α (Ra-223) or β (I-131) radionuclides to investigate the influence on vessels. TARE-induced tissue necrosis and the following neovascularization were measured by pathological analysis and 68 Ga-DOTA-RGD PET/CT. The results showed that, compared to I-131, Ra-223 enhanced the growth inhibition of human hepatoma cells Huh-7 and induced more DNA double-strand breaks in vascular smooth muscle cells. Unlike β-based TARE, which mainly led to extensive necrosis of surrounding tissues, α-based TARE induced irreversible necrosis of a limited area adjacent to the embolized vessels. RGD PET revealed the inhibition on neovascularization in α-based TARE (SUV max = 0.053 ± 0.004) when compared with normal group (SUV max = 0.099 ± 0.036), the SFMs-lipiodol group (SUV max = 0.240 ± 0.040), and β-based TARE (SUV max = 0.141 ± 0.026), owing to the avoidance of the embolism-induced neovascularization. In conclusion, α-based TARE provided a promising strategy for HCC treatments via destroying the embolized vessels and inhibiting neovascularization.