Department of Molecular Biotechnology and Health Science, University of Turin, Via Nizza 52, 10126Turin, Italy.
IRCCS SDN SynLab, Via E. Gianturco 113, 80143Napoli, Italy.
Inorg Chem. 2022 Dec 12;61(49):19663-19667. doi: 10.1021/acs.inorgchem.2c03329. Epub 2022 Nov 29.
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 H 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 P signal from endogenous inorganic phosphate (P) as the source of CEST contrast by promoting its exchange with the P bound to the exogenous complex 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (P). The herein-reported results demonstrate that this approach can improve the detectability threshold by 3 orders of magnitude with respect to the conventional H 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 (P). 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.
磁共振成像（MRI）化学交换饱和传递（CEST）对比剂领域的发展受到该技术灵敏度有限的阻碍。在水中，高质子浓度允许交换质子池的极大放大。然而，水中的 H CEST 意味着产生 CEST 的核自旋的数量必须在毫摩尔范围内。使用质子以外的核允许利用不同于水的信号，从而降低交换池的浓度作为 CEST 效应的来源。在这项工作中，我们报告了通过促进与结合到外源复合物 1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸（P）的 P 的交换，从内源性无机磷酸盐（P）作为 CEST 对比的来源来检测 P 信号。本报告的结果表明，与传统的 H CEST 检测（按单个质子计算）相比，这种方法可以将检测灵敏度提高 3 个数量级。这一成就反映了从 111.2 M（水）到 10 mM（P）检测信号的总体浓度降低。该方法为许多生物学研究和临床可转化的应用铺平了道路，在此通过细胞成像领域的概念验证来解决。
