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首页> 外文期刊>Chemistry: A European journal >MRI-guided neutron capture therapy by use of a dual gadolinium/boron agent targeted at tumour cells through upregulated low-density lipoprotein transporters
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MRI-guided neutron capture therapy by use of a dual gadolinium/boron agent targeted at tumour cells through upregulated low-density lipoprotein transporters

机译：MRI引导的中子捕获疗法，通过上调的低密度脂蛋白转运蛋白使用靶向肿瘤细胞的双重g /硼试剂

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The upregulation of low-density lipoprotein (LDL) transporters in tumour cells has been exploited to deliver a sufficient amount of gadolinium/boron/ ligand (Gd/B/L) probes for neutron capture therapy, a binary chemio-radiotherapy for cancer treatment. The Gd/B/L probe consists of a carborane unit (ten B atoms) bearing an aliphatic chain on one side (to bind LDL particles), and a Gd~(III)/1,4,7,10-tetraazacyclododecane monoamide complex on the other (for detection by magnetic resonance imaging (MRI)). Up to 190Gd/B/L probes were loaded per LDL particle. The uptake from tumour cells was initially assessed on cell cultures of human hepatoma (HepG2), murine melanoma (B16), and human glioblastoma (U87). The MRI assessment of the amount of Gd/B/L taken up by tumour cells was validated by inductively coupled plasma-mass-spectrometric measurements of the Gd and B content. Measurements were undertaken in vivo on mice bearing tumours in which B16 tumour cells were inoculated at the base of the neck. From the acquisition of magnetic resonance images, it was established that after 4-6hours from the administration of the Gd/B/L-LDL particles (0.1 and 1mmol kg~(-1) of Gd and ~(10)B, respectively) the amount of boron taken up in the tumour region is above the threshold required for successful NCT treatment. After neutron irradiation, tumour growth was followed for 20days by MRI. The group of treated mice showed markedly lower tumour growth with respect to the control group.
机译：已利用肿瘤细胞中低密度脂蛋白（LDL）转运蛋白的上调来递送足够量的g /硼/配体（Gd / B / L）探针用于中子捕获疗法，这是一种用于癌症治疗的二元化学放射疗法。 Gd / B / L探针由在一侧带有脂族链（结合LDL颗粒）的碳硼烷单元（十个B原子）和Gd〜（III）/ 1,4,7,10-四氮杂环十二烷单酰胺配合物组成另一个（用于通过磁共振成像（MRI）检测）。每个LDL粒子最多可装载190Gd / B / L探针。最初在人肝癌（HepG2），鼠黑色素瘤（B16）和人胶质母细胞瘤（U87）的细胞培养物中评估了从肿瘤细胞的摄取。 MRI对肿瘤细胞摄取的Gd / B / L量的MRI评估通过对Gd和B含量的电感耦合等离子体质谱法测量来验证。在带有肿瘤的小鼠体内进行测量，其中将B16肿瘤细胞接种在颈部的底部。从磁共振图像的获取，可以确定在施用Gd / B / L-LDL颗粒后4-6小时（分别为0.1和1mmol kg〜（-1）的Gd和〜（10）B）肿瘤区域吸收的硼量高于成功进行NCT治疗所需的阈值。中子照射后，通过MRI追踪肿瘤生长20天。与对照组相比，治疗组小鼠的肿瘤生长明显降低。

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