MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK.
Mol Imaging Biol. 2011 Aug;13(4):653-62. doi: 10.1007/s11307-010-0400-3.
This study aims to develop a low molecular weight folate receptor (FR) contrast agent for MR tumor imaging.
Gadolinium-tetraazacyclododecane tetraacetic acid (Gd.DOTA) was conjugated to folic acid to create Gd.DOTA.Folate. The efficacy of Gd.DOTA.Folate to bind FR was evaluated in vitro by inductively coupled mass spectrometry (ICP-MS) and in vivo by magnetic resonance imaging (MRI) tumor enhancement over 14 h, utilizing an overexpressing α-FR cell line (IGROV-1), compared to an α-FR-negative cell line (OVCAR-3). Gd.DOTA.Folate localization ex vivo was verified by laser ablation ICP-MS.
ICP-MS confirmed Gd.DOTA.Folate uptake by IGROV-1 cells and competitive binding with free folic acid inhibited binding. IGROV-1 tumors showed an increase in R (1) at 2 h, which increased significantly over 14 h post-Gd.DOTA.Folate with clear enhancement on MR images. This was not observed in controls.
These data support the use of FR-targeted small molecular weight MRI contrast agents for tumor imaging in vivo.
本研究旨在开发一种用于磁共振成像的低分子量叶酸受体（FR）对比剂。
将钆-四氮杂环十二烷四乙酸（Gd.DOTA）与叶酸连接，制成 Gd.DOTA.叶酸。通过电感耦合质谱（ICP-MS）体外评估 Gd.DOTA.叶酸与 FR 的结合效力，并通过磁共振成像（MRI）在 14 小时内评估肿瘤增强情况，使用过表达α-FR 的细胞系（IGROV-1）进行比较，与α-FR 阴性细胞系（OVCAR-3）进行比较。通过激光烧蚀 ICP-MS 验证 Gd.DOTA.叶酸的体外定位。
ICP-MS 证实 Gd.DOTA.叶酸被 IGROV-1 细胞摄取，游离叶酸的竞争性结合抑制了结合。IGROV-1 肿瘤在 2 小时时 R（1）增加，在 Gd.DOTA.叶酸后 14 小时内显著增加，MR 图像上有明显增强。在对照组中未观察到这种情况。
这些数据支持使用 FR 靶向的小分子 MRI 对比剂进行体内肿瘤成像。
