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

Qianqian Tong; Rou Li; Ruizhi Wang; Changjing Zuo; Danni Li; Guorong Jia; Ye Peng; Xiaohong Li; Jian Yang; Shuai Xue; Qingyun Bai; Xiao Li

doi:10.3389/fbioe.2022.1021499

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

Front Bioeng Biotechnol. 2022 Oct 7:10:1021499. doi: 10.3389/fbioe.2022.1021499. eCollection 2022.

Authors

Qianqian Tong^{1

2}, Rou Li², Ruizhi Wang³, Changjing Zuo², Danni Li², Guorong Jia², Ye Peng², Xiaohong Li², Jian Yang², Shuai Xue¹, Qingyun Bai¹, Xiao Li^{2

4}

Affiliations

¹ School of Chemistry and Bioengineering, Yichun University, Yichun, Jiangxi, China.
² Department of Nuclear Medicine, Changhai Hospital, Naval Medical University, Shanghai, China.
³ Department of Radiology, Huadong Hospital, Fudan University, Shanghai, China.
⁴ Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China.

Abstract

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 ⁶⁸Ga-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.

Keywords: Ra-223; hepatocellular carcinoma; necrosis; neovascularization; silk fibroin; transarterial radioembolization; α radionuclides.