Evaluation of the safety and efficacy of transarterial sevelamer embolization in a rabbit liver cancer model: A challenge on the size rule for vascular occlusion

Hong Chen; Chuan-Sheng Xie; Yan-Shu Li; Zhi-Qiang Deng; Yang-Feng Lv; Qiu-Chen Bi; Jian-Jun Tang; Rong-Guang Luo; Qun Tang

doi:10.3389/fbioe.2022.1058042

Evaluation of the safety and efficacy of transarterial sevelamer embolization in a rabbit liver cancer model: A challenge on the size rule for vascular occlusion

Front Bioeng Biotechnol. 2022 Dec 12:10:1058042. doi: 10.3389/fbioe.2022.1058042. eCollection 2022.

Authors

Hong Chen¹, Chuan-Sheng Xie¹, Yan-Shu Li², Zhi-Qiang Deng³, Yang-Feng Lv^{1

4}, Qiu-Chen Bi^{1

4}, Jian-Jun Tang⁵, Rong-Guang Luo⁶, Qun Tang^{1

4}

Affiliations

¹ Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China.
² Jiangxi Center of Medical Device Testing, Nanchang, China.
³ Department of Oncology, The First People's Hospital of Fuzhou, Fuzhou, China.
⁴ Institute for Advanced Study, Nanchang University, Nanchang, China.
⁵ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China.
⁶ Department of Medical Imaging and Interventional Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Abstract

As the most efficient method to treat hepatocellular carcinoma in the immediate or advanced stage, transarterial chemoembolization (TACE) is coming into the era of microsphere (MP). Drug-eluting beads have shown their huge potential as an embolic agent and drug carrier for chemoembolization, but their sizes are strictly limited to be above 40 μm, which was considered to occlude vessels in a safe mode. microsphere smaller than 40 µm is easy to be washed out and transported to the normal liver lobe or other organs, causing severe adverse events and failed embolization. To determine whether sevelamer ultrafine particle (0.2-0.5 µm) is qualified as a safe and efficient embolic agent, we investigated the safety and therapeutic efficiency of transarterial sevelamer embolization (TASE) in the VX2 rabbit liver cancer model, aiming to challenge the "40 µm" rule on the selection criteria of the MP. In a four-arm study, blank bead (Callisphere, 100-300 µm), luminescent polystyrene microsphere (10, 100 µm), and sevelamer particle were transarterially administered to evaluate the threshold size of the MP size for intrahepatic or extrahepatic permeability. Another four-arm study was designed to clarify the safety and efficiency of preclinical transarterial sevelamer embolizationTASE tests over other techniques. Sham (saline), TASE, C-TACE, and D-TACE (n = 6) were compared in terms of serum chemistry, histopathology, and tumor necrosis ratio. In the first trials, the "40 µm" rule was detectable on the VX2 cancer model, but the regulation has no application to the new embolic agent as sevelamer ultrafine particles have not been found to leak out from the VX2 lesions, only found in the embolized vessels. Pathology proves that less viable tumor residue was found 2 weeks after the procedure, evidencing a better therapeutic outcome. No adverse events were found except for a short stress response. These results indicate that sevelamer is a safe and efficient embolic as an alternative to the current MP-based embolization therapy techniques.

Keywords: VX2 carcinoma; safety; sevelamer; toxicity; transarterial chemoembolization.