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31P ParaCEST: 31P MRI-CEST Imaging Based on the Formation of a Ternary Adduct between Inorganic Phosphate and Eu-DO3A
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2022-11-29 , DOI: 10.1021/acs.inorgchem.2c03329
Giulia Vassallo 1 , Francesca Garello 1 , Silvio Aime 2 , Enzo Terreno 1 , Daniela Delli Castelli 1
Affiliation  

Development of the field of magnetic resonance imaging (MRI) chemical exchange saturation transfer (CEST) contrast agents is hampered by the limited sensitivity of the technique. In water, the high proton concentration allows for an enormous amplification of the exchanging proton pool. However, the 1H CEST in water implies that the number of nuclear spins of the CEST-generating species has to be in the millimolar range. The use of nuclei other than a proton allows exploitation of signals different from that of water, thus lowering the concentration of the exchanging pool as the source of the CEST effect. In this work, we report on the detection of a 31P signal from endogenous inorganic phosphate (Pifree) as the source of CEST contrast by promoting its exchange with the Pi bound to the exogenous complex 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (Pibound). The herein-reported results demonstrate that this approach can improve the detectability threshold by 3 orders of magnitude with respect to the conventional 1H CEST detection (considered per single proton). This achievement reflects the decrease of the bulk concentration of the detected signal from 111.2 M (water) to 10 mM (Pi). This method paves the way to a number of biological studies and clinically translatable applications, herein addressed with a proof-of-concept in the field of cellular imaging.

中文翻译:


31P ParaCEST:基于无机磷酸盐和 Eu-DO3A 之间三元加合物形成的 31P MRI-CEST 成像



磁共振成像(MRI)化学交换饱和转移(CEST)造影剂领域的发展因技术灵敏度有限而受到阻碍。在水中,高质子浓度可以极大地放大交换质子池。然而,水中的1 H CEST 意味着产生 CEST 的物质的核自旋数必须在毫摩尔范围内。使用质子以外的原子核可以利用与水不同的信号,从而降低作为 CEST 效应来源的交换池的浓度。在这项工作中,我们报告了通过促进内源性无机磷酸盐(无磷)与外源复合物 1,4,7,10-四氮杂环十二烷-结合的 P 的交换来检测作为 CEST 对比来源的31 P 信号。 1,4,7-三乙酸(P结合)。本文报告的结果表明,相对于传统的1 H CEST 检测(按单个质子考虑),该方法可以将可检测性阈值提高 3 个数量级。这一成就反映了检测到的信号的总体浓度从 111.2 M(水)降低至 10 mM(P)。该方法为许多生物学研究和临床可转化应用铺平了道路,本文通过细胞成像领域的概念验证来解决。
更新日期:2022-11-29
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