Department of Molecular Biotechnology and Health Sciences; University of Torino, via Nizza 52, Torino 10126, Italy.
Department of Chemistry, University of Torino, via Pietro Giuria 7, Torino 10125, Italy.
J Control Release. 2018 Jun 28;280:31-38. doi: 10.1016/j.jconrel.2018.04.043. Epub 2018 May 3.
The aim of this study is to develop an innovative imaging guided approach based on Boron Neutron Capture Therapy, for the treatment of mesothelioma, assisted by the quantification of the in vivo boron distribution by MRI. The herein reported results demonstrate that overexpressed Low Density Lipoproteins receptors can be successfully exploited to deliver to mesothelioma cells a therapeutic dose of boron (26 μg/g), significantly higher than in the surrounding tissue (3.5 μg/g). Boron and Gd cells uptake was assessed by ICP-MS and MRI on two mesothelioma (ZL34, AE17) and two healthy (MRC-5 and NMuMg) cell lines. An in vivo model was prepared by subcutaneous injection of ZL34 cells in Nu/Nu mice. After irradiation with thermal neutrons, tumor growth was evaluated for 40 days by MRI. Tumor masses of boron treated mice showed a drastic reduction of about 80-85%. The obtained results appear very promising providing patients affected by this rare disease with an improved therapeutic option, exploiting LDL transporters.
本研究旨在开发一种基于硼中子俘获治疗的创新影像引导方法，通过 MRI 对体内硼分布进行定量，辅助治疗间皮瘤。本研究报告的结果表明，过表达的低密度脂蛋白受体可成功用于向间皮瘤细胞输送治疗剂量的硼（26μg/g），显著高于周围组织（3.5μg/g）。通过电感耦合等离子体质谱法（ICP-MS）和 MRI 评估了两种间皮瘤（ZL34、AE17）和两种正常细胞系（MRC-5 和 NMuMg）的硼和 Gd 细胞摄取。通过皮下注射 ZL34 细胞在 Nu/Nu 小鼠中制备体内模型。用热中子照射后，通过 MRI 评估肿瘤生长 40 天。硼处理小鼠的肿瘤质量明显减少了约 80-85%。获得的结果非常有前景，为患有这种罕见疾病的患者提供了一种改进的治疗选择，利用 LDL 转运体。
