Alberti Diego, Protti Nicoletta, Toppino Antonio, Deagostino Annamaria, Lanzardo Stefania, Bortolussi Silva, Altieri Saverio, Voena Claudia, Chiarle Roberto, Geninatti Crich Simonetta, Aime Silvio
Department of Molecular Biotechnology and Health Sciences; University of Torino, Torino, Italy.
Department of Nuclear and Theoretical Physics, University of Pavia, Pavia, Italy; Nuclear Physics National Institute (INFN), section of Pavia, Pavia, Italy.
Nanomedicine. 2015 Apr;11(3):741-50. doi: 10.1016/j.nano.2014.12.004. Epub 2015 Jan 14.
This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation.
本研究旨在基于硼中子俘获疗法（BNCT）开发一种用于肺癌肿瘤及转移灶治疗的创新型诊疗方法。它依赖于使用低密度脂蛋白（LDL）作为载体，这种载体能够使硼原子在肿瘤细胞中的选择性摄取最大化，同时通过磁共振成像（MRI）对体内硼分布进行定量分析。最初通过电感耦合等离子体质谱（ICP-MS）和MRI对四种肿瘤细胞系（TUBO、B16-F10、MCF-7、A549）和一种健康细胞系（N-MUG）评估肿瘤细胞摄取情况。通过向BALB/c小鼠静脉注射Her2+乳腺癌细胞系（即TUBO）产生肺转移灶，并将转基因EML4-ALK小鼠用作原发性肿瘤模型。中子辐照后，通过MRI对肿瘤生长情况进行30至40天的跟踪观察。硼处理组小鼠的肿瘤块增长明显比对照组缓慢。临床编辑点评：在本文中，作者描述了对现有硼中子俘获疗法的一种改进。由LDL携带的双功能MRI/BNCT剂能够使硼在肿瘤细胞中的选择性摄取最大化，同时利用MRI对肿瘤及其他组织中的硼分布进行定量分析。随后的体外和体内实验表明中子辐照后肿瘤细胞被杀伤。
