Design and characterization of a new irreversible responsive PARACEST MRI contrast agent that detects nitric oxide
Design and characterization of a new irreversible responsive PARACEST MRI contrast agent that detects nitric oxide
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DOI：
10.1002/mrm.21428
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发表时间：
2007-12-01
影响因子：
3.3
通讯作者：
Pagel, Mark D.
中科院分区：
文献类型：
--
作者：
Liu, Guanshu;Li, Yuguo;Pagel, Mark D.
不可逆的响应式顺磁化学交换转移（Paracest）MRI对比剂构成了一种用于分子成像的新型药物。为了调查这种方法的实用性，一种新型最偏执的MRI对比剂YB（iii） - （1,4,7,10-tetraazacyClododecane-1,4,7-乙酸） - 北氨基烷（YB-DO3A-OAA），开发了检测一氧化氮（NO）的开发。该试剂在-11 ppm和+8 ppm时表现出两个CEST效应，分别分别从酰胺和胺官能团分配给化学交换。研究了pH，温度和浓度的作用，以表征复合物并优化最高的检测。这种反应敏感的最偏见的MRI对比剂在NO和02的存在下产生了不可逆的共价变化，这导致MR图像的两种偏见作用都无法可逆地消失。研究了基于松弛性的MRI对比剂GD-DO3A-OAA的无依赖性响应，以进行比较。该报告强调了不可逆的MRI对比剂的优势，证明了最有用的最大变化可用于创建高度响应的剂，并表明必须克服挑战才能将这种类型的对比剂应用于分子成像中的体内生物医学应用。
Irreversible responsive PARAmagnetic Chemical Exchange Saturation Transfer (PARACEST) MRI contrast agents constitute a new type of agent for molecular imaging. To investigate the utility of this approach, a novel PARACEST MRI contrast agent, Yb(III)-(1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid)-orthoaminoanilide (Yb-DO3A-oAA), was developed that detects nitric oxide (NO). The agent exhibited two CEST effects at -11 ppm and +8 ppm, which were assigned to chemical exchange from amide and amine functional groups, respectively. The effects of pH, temperature, and concentration were investigated to characterize the complex and to optimize PARACEST detection. This responsive PARACEST MRI contrast agent incurred an irreversible covalent change in the presence of NO and 02, which caused an irreversible disappearance of both PARACEST effects from MR images. The NO-dependent response of a relaxivity-based MRI contrast agent, Gd-DO3A-oAA, was investigated for comparison. This report highlights the advantages of irreversible MRI contrast agents, demonstrates that large changes in PARACEST can be used to create a highly responsive agent, and indicates challenges that must be overcome to apply this type of contrast agent to in vivo biomedical applications in molecular imaging.