Dual-modality gene reporter for in vivo imaging
Dual-modality gene reporter for in vivo imaging
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DOI：
10.1073/pnas.1319000111
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发表时间：
2014-01-07
影响因子：
11.1
通讯作者：
Brindle, Kevin M.
中科院分区：
文献类型：
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作者：
Patrick, P. Stephen;Hammersley, Jayne;Brindle, Kevin M.
跟踪活生物体中细胞及其基因表达模式的能力可以增加我们对组织发育和疾病的理解。已经描述了用于生物发光、荧光、放射性核素和磁共振成像（MRI）的基因报告物，但是这些基因报告物受到不同程度的有限深度穿透、空间分辨率和灵敏度的影响。我们在这里描述了一个基因报告，基于有机阴离子转运蛋白Oatp 1a 1，介导摄取的临床批准的，Gd 3+为基础的，肝造影剂（钆-乙氧基苄基二亚乙基三胺五乙酸）。在体内获得的T-1加权磁共振图像中，表达报告基因的细胞显示出容易可逆的、强烈的和阳性的对比度（高达7.8倍的信号增强）。迄今为止获得的最大信号增强是先前描述的MRI基因报告者产生的信号增强的两倍以上。将Gd 3+离子交换为放射性核素In-111也允许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相结合。
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, Gd3+-based, hepatotrophic contrast agent (gadolinium-ethoxybenzyldiethylenetriamine pentaacetic acid). Cells expressing the reporter showed readily reversible, intense, and positive contrast (up to 7.8-fold signal enhancement) in T-1-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 Gd3+ ion for the radionuclide, In-111, also allowed detection by single-photon emission computed tomography, thus combining the spatial resolution of MRI with the sensitivity of radionuclide imaging.