Bogdanov Alexei, Matuszewski Lars, Bremer Christoph, Petrovsky Alexander, Weissleder Ralph
Center for Molecular Imaging Research, Massachusetts General Hospital, CNY-5, Rm. 5420, Building 149, 13th Street, Charlestown, MA 02129, USA.
Mol Imaging. 2002 Jan-Mar;1(1):16-23. doi: 10.1162/15353500200200001.
Magnetic resonance imaging (MRI) has evolved into a sophisticated, noninvasive imaging modality capable of high-resolution anatomical and functional characterization of transgenic animals. To expand the capabilities MRI, we have developed a novel MR signal amplification (MRamp) strategy based on enzyme-mediated polymerization of paramagnetic substrates into oligomers of higher magnetic relaxtivity. The substrates consist of chelated gadolinium covalently bound to phenols, which then serve as electron donors during enzymatic hydrogen peroxide reduction by peroxidase. The converted monomers undergo rapid condensation into paramagnetic oligomers leading to a threefold increase in atomic relaxtivity (R1/Gd). The observed relaxtivity changes are largely due to an increase in the rotational correlation time tau r of the lanthanide. Three applications of the developed system are demonstrated: (1) imaging of nanomolar amounts of an oxidoreductase (peroxidase); (2) detection of a model ligand using an enzyme-linked immunoadsorbent assay format; and (3) imaging of E-selectin on the surface of endothelial cells probed for with an anti-E-selectin-peroxidase conjugate. The development of "enzyme sensing" probes is expected to have utility for a number of applications including in vivo detection of specific molecular targets. One particular advantage of the MRamp technique is that the same paramagnetic substrate can be potentially used to identify different molecular targets by attaching enzymes to various antibodies or other target-seeking molecules.
磁共振成像（MRI）已发展成为一种复杂的非侵入性成像方式，能够对转基因动物进行高分辨率的解剖学和功能特征分析。为了扩展MRI的功能，我们开发了一种基于酶介导的顺磁性底物聚合成具有更高磁弛豫率的低聚物的新型磁共振信号放大（MRamp）策略。底物由与酚共价结合的螯合钆组成，在过氧化物酶催化过氧化氢还原过程中，酚作为电子供体。转化后的单体迅速缩合形成顺磁性低聚物，导致原子弛豫率（R1/Gd）增加三倍。观察到的弛豫率变化主要是由于镧系元素的旋转相关时间tau r增加。展示了所开发系统的三个应用：（1）对纳摩尔量的氧化还原酶（过氧化物酶）进行成像；（2）使用酶联免疫吸附测定形式检测模型配体；（3）用抗E选择素-过氧化物酶偶联物探测内皮细胞表面的E选择素成像。“酶传感”探针的开发有望用于包括体内检测特定分子靶点在内的许多应用。MRamp技术的一个特别优点是，通过将酶连接到各种抗体或其他寻靶分子上，相同的顺磁性底物可能用于识别不同的分子靶点。
