Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.
Hepatology Program, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.
Sci Rep. 2022 Feb 2;12(1):1777. doi: 10.1038/s41598-022-05672-3.
Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy-hypertrophy complex after SIRT. Three groups of 5-8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with different activities (0.3, 0.6 and 1.2 GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2 GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6 GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced significant toxicity. Cranial SIRT with 0.3 GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2 GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3 GBq groups developed moderate damage with inflammation and portal fibrosis at 15 days, partially recovering at 30 days. There was no difference in the expression of hepatocyte function and differentiation genes between 0.3 GBq and control groups. Cranial SIRT with 0.3 GBq of Y resin microspheres in rabbits is a reliable animal model to analyse the atrophy-hypertrophy complex and liver damage without toxicity.
叶段选择性内放射治疗（SIRT）广泛用于治疗肝脏肿瘤，导致治疗叶萎缩和对侧肥大。由于缺乏动物模型，进一步的研究受到限制，无法改进这种治疗方法。我们开发了一种 SIRT 后肝脏损伤和萎缩-肥大复合模型的动物模型。三组 5-8 只兔子接受经门静脉 SIRT，使用钇 90 树脂微球，放射性活度分别为 0.3、0.6 和 1.2GBq，分别对应预测吸收辐射剂量 200、400 和 800Gy。另一组接受无载微球（假手术组）。SIRT 前、后 15 天和 30 天，使用 CT 体层摄影术评估颅叶和尾叶的体积。评估肝生化、组织病理学和基因表达。另外 4 只未治疗的兔子作为基因表达研究的对照。由于临床恶化，所有接受 1.2GBq 的动物均被安乐死。颅 SIRT 用 0.6GBq 在 15 天后引起尾叶肥大（中位数增加 34%，无统计学意义），但产生明显的毒性。颅 SIRT 用 0.3GBq 在 30 天后引起尾叶肥大（中位数增加 82%，p=0.04）。假手术组未发现体积变化。所有治疗组的血清转氨酶均短暂升高，15 天后恢复正常。随着胆红素升高和白蛋白减少，肝功能呈剂量依赖性下降。组织学上，1.2GBq 组在 15 天出现永久性严重肝损伤，伴有大量坏死，0.6 和 0.3GBq 组在 15 天出现中度损伤，伴有炎症和门脉纤维化，30 天部分恢复。0.3GBq 组与对照组之间，肝细胞功能和分化基因的表达无差异。在兔子中，使用 0.3GBq 的 Y 树脂微球进行颅 SIRT 是一种可靠的动物模型，可在无毒性的情况下分析萎缩-肥大复合和肝损伤。
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