Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):415-20. doi: 10.1073/pnas.1319000111. Epub 2013 Dec 17.
The ability to track cells and their patterns of gene expression in living organisms can increase our understanding of tissue development and disease. Gene reporters for bioluminescence, fluorescence, radionuclide, and magnetic resonance imaging (MRI) have been described but these suffer variously from limited depth penetration, spatial resolution, and sensitivity. We describe here a gene reporter, based on the organic anion transporting protein Oatp1a1, which mediates uptake of a clinically approved, Gd(3+)-based, hepatotrophic contrast agent (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid). Cells expressing the reporter showed readily reversible, intense, and positive contrast (up to 7.8-fold signal enhancement) in T1-weighted magnetic resonance images acquired in vivo. The maximum signal enhancement obtained so far is more than double that produced by MRI gene reporters described previously. Exchanging the Gd(3+) ion for the radionuclide, (111)In, also allowed detection by single-photon emission computed tomography, thus combining the spatial resolution of MRI with the sensitivity of radionuclide imaging.
能够在活体生物中追踪细胞及其基因表达模式，可以增进我们对组织发育和疾病的了解。已经有用于生物发光、荧光、放射性核素和磁共振成像（MRI）的基因报告基因，但这些方法在深度穿透、空间分辨率和灵敏度方面存在各种局限性。我们在这里描述了一种基于有机阴离子转运蛋白 Oatp1a1 的基因报告基因，该基因报告基因介导摄取一种临床批准的、基于 Gd（3+）的肝靶向对比剂（钆乙氧基苯二乙酸二乙三胺五乙酸）。表达报告基因的细胞在体内获得的 T1 加权磁共振图像中显示出可逆转、强烈和阳性的对比（高达 7.8 倍的信号增强）。迄今为止获得的最大信号增强是以前描述的 MRI 基因报告基因产生的两倍多。将 Gd（3+）离子交换为放射性核素（111）In，也可以通过单光子发射计算机断层扫描进行检测，从而将 MRI 的空间分辨率与放射性核素成像的灵敏度结合起来。
