Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent.
Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent.
复制标题
DOI：
10.1021/acs.bioconjchem.5b00561
复制
发表时间：
2016-02-17
影响因子：
4.7
通讯作者：
Meade TJ
中科院分区：
文献类型：
--
作者：
MacRenaris KW;Ma Z;Krueger RL;Carney CE;Meade TJ
钙 [Ca(II)] 是中枢神经系统 (CNS) 电活动的基本传感器。 Ca(II) 流入细胞质负责动作电位的启动和传播，并通过释放神经递质和激活基因表达来启动神经元间通讯。尽管 Ca(II) 在生理学中很重要，但体内中枢神经系统 (CNS) 中 Ca(II) 通量的可视化仍然是一个挑战。为了应对这些挑战，我们开发了新一代 Ca(II) 激活 MRI 造影剂，它利用乙酯来增加细胞标记并防止细胞外二价 Ca(II) 结合。标记后，乙酯可以裂解，从而使试剂与 Ca(II) 结合，增加弛豫度并导致增强的正 MR 图像对比度。该探针区分细胞外和细胞内 Ca(II) 的能力可能允许在癫痫或缺血期间对 Ca(II) 通量进行时空体内成像，其中大 Ca(II) 通量 (1–10 μM) 可导致细胞死亡。
Calcium [Ca(II)] is a fundamental transducer of electrical activity in the central nervous system (CNS). Influx of Ca(II) into the cytosol is responsible for action potential initiation and propagation, and initiates interneuronal communication via release of neurotransmitters and activation of gene expression. Despite the importance of Ca(II) in physiology, it remains a challenge to visualize Ca(II) flux in the central nervous system (CNS) in vivo. To address these challenges, we have developed a new generation, Ca(II)-activated MRI contrast agent that utilizes ethyl esters to increase cell labeling and prevent extracellular divalent Ca(II) binding. Following labeling, the ethyl esters can be cleaved, thus allowing the agent to bind Ca(II), increasing relaxivity and resulting in enhanced positive MR image contrast. The ability of this probe to discriminate between extra- and intracellular Ca(II) may allow for spatiotemporal in vivo imaging of Ca(II) flux during seizures or ischemia where large Ca(II) fluxes (1–10 μM) can result in cell death.