Responsive MRI agents for sensing metabolism in vivo.
Responsive MRI agents for sensing metabolism in vivo.
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DOI：
10.1021/ar800237f
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发表时间：
2009-07-21
影响因子：
18.3
通讯作者：
Sherry, A. Dean
中科院分区：
文献类型：
--
作者：
De Leon-Rodriguez, Luis M.;Lubag, Angelo Josue M.;Malloy, Craig R.;Martinez, Gary V.;Gillies, Robert J.;Sherry, A. Dean
与光学和放射性示踪成像方法相比，磁共振成像（MRI）在安全性、三维输出和临床相关性方面具有固有优势。然而，MRI造影剂本质上不如其他成像模式中使用的造影剂敏感，这主要是因为MRI造影剂是通过水质子弛豫率（T1、T2和T2*）或水质子强度（化学交换饱和转移和顺磁性化学交换饱和转移，CEST和PARACEST）的变化间接检测的。因此，MRI造影剂的检测限由背景水信号的特征决定；相比之下，基于光学和放射性示踪的方法允许直接检测造影剂本身。然而，由于对背景水（其反映了细胞整体特性）有响应，MRI造影剂在“代谢”成像方面具有相当大的优势——即对组织的pH值、氧化还原状态、氧合或代谢物水平的空间变化进行分辨。在本文中，我们首先研究靶向造影剂的灵敏度极限，然后探讨对生理变化有响应的造影剂；这些响应性造影剂是有效的代谢成像传感器。
代谢成像造影剂的灵敏度要求与基于靶向Gd3+的T1造影剂（例如用于检测细胞受体）有很大不同。靶向Gd3+造影剂必须具有极高的水质子弛豫率（r1），或者在聚合物平台或纳米颗粒组装体上的靶点处聚集多个Gd3+复合物。代谢MRI造影剂的不同之处在于，高弛豫率要求虽然有帮助，但有所放宽，因为这些造影剂是对组织的整体特性而非低浓度的特定生物靶点有响应。为了实现最佳检测，代谢成像造影剂应该在对感兴趣的生理或代谢参数有响应时显示出弛豫率的大幅变化（Δr1）。
代谢成像造影剂最近才开始在文献中出现，并且只有少数在体内得到了验证。已经使用基于Gd3+的T1传感器获得了绝对组织pH的MRI图谱。在组织中对造影剂浓度进行独立测量的要求使这些实验变得复杂，但如果组织pH的定性变化是可以接受的，那么这些造影剂可能非常有用。最后，我们描述了使用基于Gd3+的pH传感器对脑肿瘤、缺血心脏和胰岛中的细胞外pH进行成像的实例，并讨论了CEST和PARACEST造影剂作为代谢成像传感器的潜力。
Magnetic resonance imaging (MRI) has inherent advantages in safety, three-dimensional output, and clinical relevance when compared with optical and radiotracer imaging methods. However, MRI contrast agents are inherently less sensitive than agents used in other imaging modalities primarily because MRI agents are detected indirectly by changes in either the water proton relaxation rates (T1, T2, and T2 *) or water proton intensities (chemical exchange saturation transfer and paramagnetic chemical exchange saturation transfer, CEST and PARACEST). Consequently, the detection limit of an MRI agent is determined by the characteristics of the background water signal; by contrast, optical and radiotracer-based methods permit direct detection of the agent itself. By virtue of responding to background water (which reflects bulk cell properties), however, MRI contrast agents have considerable advantages in "metabolic" imaging—that is, spatially resolving tissue variations in pH, redox state, oxygenation, or metabolite levels. In this Account, we begin by examining sensitivity limits in targeted contrast agents and then address contrast agents that respond to a physiological change; these responsive agents are effective metabolic imaging sensors. The sensitivity requirements for a metabolic imaging agent are quite different from those for a targeted Gd3+-based T1 agent (for sensing cell receptors, for example). Targeted Gd3+ agents must have either an extraordinarily high water proton relaxivity (r1) or multiple Gd3+ complexes clustered together at the target site on a polymer platform or nanoparticle assembly. Metabolic MRI agents differ in that the high relaxivity requirement, although helpful, is eased because these agents respond to bulk properties of tissues rather than low concentrations of a specific biological target. For optimal sensing, metabolic imaging agents should display a large change in relaxivity (Δr1) in response to the physiological or metabolic parameter of interest. Metabolic imaging agents have only recently begun to appear in the literature and only a few have been demonstrated in vivo. MRI maps of absolute tissue pH have been obtained with Gd3+-based T1 sensors. The requirement of an independent measure of agent concentration in tissues complicates these experiments, but if qualitative changes in tissue pH are acceptable, then these agents can be quite useful. Finally, we describe examples of imaging extracellular pH in brain tumors, ischemic hearts, and pancreatic islets with Gd3+-based pH sensors and discuss the potential of CEST and PARACEST agents as metabolic imaging sensors.
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影响因子：
2.5
作者：
Hanaoka, Kenjiro;Lubag, Angelo Josue M.;Sherry, A. Dean
通讯作者：
Sherry, A. Dean
影响因子：
5.5
作者：
Chen, W;Tomalia, DA;Thomas, JL
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影响因子：
4.3
作者：
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影响因子：
15
作者：
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通讯作者：
Kodadek, Thomas
影响因子：
2.2
作者：
Ward, KM;Aletras, AH;Balaban, RS
通讯作者：
Balaban, RS