Department of Surgery and Radiology and Physical Medicine, University of The Basque Country (UPV/EHU), Leioa, Spain,
Biocruces Bizkaia Health Research Institute, Barakaldo, Spain,
Eur Surg Res. 2020;61(4-5):136-142. doi: 10.1159/000512458. Epub 2020 Dec 17.
Nowadays, surgical excision remains the gold standard to treat liver metastases of colorectal cancer (CRCLM). However, as more than 50% of patients are not eligible for surgery, other alternatives such as percutaneous or intravascular interventional therapies (thermal ablation, chemoembolization, or radioembolization), are quite relevant. Recently, the use of magnetic nanoparticles (MNPs) has been suggested as an adjuvant for these therapies, as they could increase their necrotising effect on the tumour while reducing doses and exposure times of thermal therapies. To investigate the potential curative effect of these compounds, animal models are needed, both for the development of experimental interventional procedures and for MNPs toxicity and distribution assessment. Herein, we describe both an experimental infusion procedure in CRCLM-bearing rats and analytical and histological methods to evaluate MNPs deposits in the tissue.
Eighteen male WAG/RijHsd rats were subjected to intrahepatic injection of 250,000 colorectal cancer cells. Twenty-eight days later, half of the tumour-positive animals (n = 6) were administered with MNPs while the other half (n = 6) did not receive any injection and were used as control. Under microscope magnification, the splenic artery was carefully and completely dissected, and a catheter was inserted through the splenic artery to the common hepatic artery where 1 mL MNPs suspension was administered in 5 min; then STIR, DP*, and T2 MRI sequences were obtained (and signal intensity measured) and both tumour and liver tissue samples were collected for elemental and histological analyses.
Our method for selective administration of MNPs is reproducible and well-tolerated and it fairly mimics the approach used in clinical practice when intravascular interventional therapies are applied.
如今，手术切除仍然是治疗结直肠癌肝转移（CRCLM）的金标准。然而，由于超过 50%的患者不符合手术条件，因此其他替代方法，如经皮或血管内介入治疗（热消融、化疗栓塞或放射性栓塞），则相当相关。最近，磁性纳米粒子（MNPs）的应用被认为是这些疗法的辅助手段，因为它们可以在增加肿瘤坏死作用的同时，减少热疗的剂量和暴露时间。为了研究这些化合物的潜在疗效，需要动物模型，既用于实验性介入手术的开发，也用于 MNPs 毒性和分布评估。在此，我们描述了一种在患有 CRCLM 的大鼠中进行的实验性输注程序，以及用于评估组织中 MNPs 沉积的分析和组织学方法。
18 只雄性 WAG/RijHsd 大鼠接受了 250,000 个结直肠癌细胞的肝内注射。28 天后，一半肿瘤阳性动物（n = 6）接受了 MNPs 治疗，而另一半（n = 6）未接受任何注射，用作对照。在显微镜放大下，小心且完全解剖脾动脉，并通过脾动脉插入导管至肝总动脉，在 5 分钟内注入 1 毫升 MNPs 混悬液；然后获得 STIR、DP*和 T2 MRI 序列（并测量信号强度），并收集肿瘤和肝脏组织样本进行元素和组织学分析。
我们用于选择性给予 MNPs 的方法是可重复和耐受良好的，并且它相当模拟了在应用血管内介入治疗时在临床实践中使用的方法。
