Bioresponsive, cell-penetrating, and multimeric MR contrast agents.
Bioresponsive, cell-penetrating, and multimeric MR contrast agents.
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DOI：
10.1021/ar800245h
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发表时间：
2009-07-21
影响因子：
18.3
通讯作者：
Meade, Thomas J.
中科院分区：
文献类型：
--
作者：
Major, Jody L.;Meade, Thomas J.
磁共振成像(MRI)是一种非侵入性的非侵入性成像技术，能够产生高时空分辨率的不透明生物的三维图像，因此在分子成像和临床放射学领域得到了越来越广泛的应用。虽然大约35%的临床磁共振扫描使用造影剂，但磁共振成像的一个主要限制是检测需要高浓度造影剂以增强信号强度(0.1-0.6 mm)的低灵敏度。已经采用了许多策略来放大MR造影剂的体内观察信号。方法包括将Gd(III)螯合物附着到聚合物、蛋白质和颗粒上，将其包裹到胶束和笼状结构中，以及靶向受体。虽然这些方法中的每一种都显著增加了MR造影剂的弛豫度(因此灵敏度)，但所有这些类型的复合体都具有内在的背景信号，并且由于它们的结构性活性而仅作为解剖学报告发挥作用。为了减少背景信号，同时产生受生化事件调制的探针，笼状络合物被设计成配位饱和顺磁离子。与扩增策略相结合，这些试剂代表了一种选择性地调制观察到的MR信号的方法，并作为体内生化报告发挥作用。例如，为了建立酶活性和二级信使的体内MR分析，已经设计和合成了带有可拆卸保护基团的试剂，这些保护基团在很大程度上阻止了水进入顺磁中心。通过限制散装水的进入(调Q)，未经处理的试剂被设计为无效的造影剂，因此可以作为酶活性区域或二级信使的可靠标记。在这篇文章中，我们描述了我们在设计新的类MR试剂方面的结果，这些试剂是I对体内生理或生化事件的反应II。细胞渗透性，以增加局部浓度，以及III。附着在大分子上或与多个标记的共轭化合物合成以用于信号放大。
Magnetic resonance imaging (MRI) has become increasingly popular in molecular imaging and clinical radiology because it is non-invasive and capable of producing three-dimensional representations of opaque organisms with high spatial and temporal resolution. While approximately 35% of all clinical MR scans utilize contrast media, a primary limitation of MR imaging is the low sensitivity to detect contrast agents requiring high concentrations of agent for enhanced signal intensity (0.1-0.6 mM). A number of strategies have been employed to amplify the observed in vivo signal of MR contrast agents. Approaches include attachment of Gd(III) chelates to polymers, proteins and particles, encapsulation into micelles and caged structures, and targeting to receptors. While each of these approaches has yielded significant increases in the relaxivity of MR contrast agents (and therefore sensitivity), all of these classes of complexes possess intrinsic background signal and function solely as anatomical reporters due to their constitutive activity. In order to reduce the background signal and simultaneously create probes that are modulated by biochemical events, caged complexes were designed to coordinatively saturate the paramagnetic ion. Coupled with amplification strategies, these agents represent a means to selectively modulate the observed MR signal and function as in vivo biochemical reporters. For example, to create an in vivo MR assay of enzymatic activities and secondary messengers, agents have been designed and synthesized with removable protection groups that largely prevent access of water to a paramagnetic center. By limiting the access of bulk water (q-modulation) the unprocessed agent is designed to be an ineffective contrast agent, and hence serves as a reliable marker for regions of enzyme activity or secondary messengers. In this Account we describe our results toward designing new classes of MR agents that are i. responsive to in vivo physiological or biochemical events ii. cell-permeable to increase local concentration, and iii. attached to large molecules or are synthesized with multiply labeled conjugates for signal amplification.
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影响因子：
4.7
作者：
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通讯作者：
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