Fe-HBED Analogs: A Promising Class of Iron-Chelate Contrast Agents for Magnetic Resonance Imaging
Fe-HBED Analogs: A Promising Class of Iron-Chelate Contrast Agents for Magnetic Resonance Imaging
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DOI：
10.1155/2019/8356931
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发表时间：
2019-12-20
影响因子：
--
通讯作者：
Roberts, Jeannette
中科院分区：
文献类型：
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作者：
Bales, Brian C.;Grimmond, Brian;Roberts, Jeannette
对比增强磁共振成像是疾病诊断和管理的重要工具;所有市售的临床磁共振成像（MRI）造影剂（CA）均为钆（Gd）螯合物，大多数为细胞外液（ECF）试剂。静脉注射后，这些药物迅速分布到细胞外空间，其特征还在于低血清蛋白结合和主要的肾清除。Gd是一种非生物元素，没有生物再循环过程;在给药后很长时间内，在中枢神经系统和骨骼中检测到低水平的Gd。这些观察结果促使人们对开发基于生物元素如铁（Fe）的新型MRI造影剂产生兴趣; Fe-HBED（HBED = N，N ′-双（2-羟基苯基）乙二胺-N，N ′-二乙酸），一种配位饱和的铁螯合物，是一种有吸引力的MRI CA平台，适合于修饰以调节弛豫率和生物分布。与母体Fe-HBED相比，本文报道的Fe-HBED类似物在小鼠中具有较低的血清蛋白结合和较高的弛豫率以及较低的相对肝脏增强，与代表性的钆基造影剂（GBCA）相当。因此，Fe-HBED类似物是一类有前途的非Gd ECF MRI CA。
Contrast-enhanced magnetic resonance imaging is an essential tool for disease diagnosis and management; all marketed clinical magnetic resonance imaging (MRI) contrast agents (CAs) are gadolinium (Gd) chelates and most are extracellular fluid (ECF) agents. After intravenous injection, these agents rapidly distribute to the extracellular space and are also characterized by low serum protein binding and predominant renal clearance. Gd is an abiotic element with no biological recycling processes; low levels of Gd have been detected in the central nervous system and bone long after administration. These observations have prompted interest in the development of new MRI contrast agents based on biotic elements such as iron (Fe); Fe-HBED (HBED = N,N '-bis(2-hydroxyphenyl)ethylenediamine-N,N '-diacetic acid), a coordinatively saturated iron chelate, is an attractive MRI CA platform suitable for modification to adjust relaxivity and biodistribution. Compared to the parent Fe-HBED, the Fe-HBED analogs reported here have lower serum protein binding and higher relaxivity as well as lower relative liver enhancement in mice, comparable to that of a representative gadolinium-based contrast agent (GBCA). Fe-HBED analogs are therefore a promising class of non-Gd ECF MRI CA.