The NiCEST Approach: Nickel(II) ParaCEST MRI Contrast Agents
The NiCEST Approach: Nickel(II) ParaCEST MRI Contrast Agents
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DOI：
10.1021/ja307909x
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发表时间：
2012-11-14
影响因子：
15
通讯作者：
Morrow, Janet R.
中科院分区：
文献类型：
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作者：
Olatunde, Abiola O.;Dorazio, Sarina J.;Morrow, Janet R.
顺磁性Ni（II）络合物在此显示为形成paraCEST MRI造影剂（paraCEST =顺磁性：化学交换饱和转移; NICEST =基于Ni（II）的CEST试剂）。具有酰胺侧基的三个氮杂大环结合Ni（II）以形成稳定的NiCEST造影剂，包括1，4，7-三-（氨基甲酰基甲基）-1，4，7-三氮杂环壬烷。(L1)1，4，8，11-四（氨甲酰基甲基）-1，4，8，11-四氮杂环十四烷（L2）和7，13-双（氨甲酰基甲基）-1，4，10-三氧杂-7，13-二氮杂环十五烷（L3）。[Ni（L3）]（2+）、[Ni（L1）]（2+）和[Ni（L2）]（2+）具有归因于酰胺质子的CEST峰，其分别从本体水共振偏移72、76和76 ppm。CEST MR图像和CEST光谱均显示，在37 ℃下，[Ni（L3）]（2+）在100 mM NaCl、20 mM HEPES pH 7.4中具有最大的CEST效应。这种较大的CEST效应归因于络合物的较尖锐的质子共振，其产生于刚性结构和低弛豫率。
Paramagnetic Ni(II) complexes are shown here to form paraCEST MRI contrast agents (paraCEST = paramagnetic: chemical exchange saturation transfer; NICEST = Ni(II) based CEST agents). Three azamacro-cycles with amide pendent groups bind Ni(II) to form stable NiCEST contrast agents including 1,4,7-tris-(carbamoylmethyl)-1,4,7-triazacyclononane. (L1), 1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclo-tetradecane (L2), and 7,13-bis(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (L3). [Ni(L3)](2+), [Ni(L1)](2+), and [Ni(L2)](2+) have CEST peaks attributed to amide protons that are shifted 72, 76, and 76 ppm from the bulk water resonance, respectively. Both CEST MR images and CEST spectroscopy show that [Ni(L3)](2+) has the largest CEST effect in 100 mM NaCl, 20 mM HEPES pH 7.4 at 37 degrees C. This larger CEST effect is attributed to the sharper proton resonances of the complex which arise from a rigid structure and low relaxivity.