Department of Organic Chemistry, Faculty of Chemistry, Weizmann Institute of Science, Rehovot, 7610001, Israel.
Department of Chemical Research Support, Faculty of Chemistry, Weizmann Institute of Science, Rehovot, 7610001, Israel.
Angew Chem Int Ed Engl. 2021 Jul 5;60(28):15405-15411. doi: 10.1002/anie.202100427. Epub 2021 Jun 4.
The weak thermal polarization of nuclear spins limits the sensitivity of MRI, even for MR-sensitive nuclei as fluorine-19. Therefore, despite being the source of inspiration for the development of background-free MRI for various applications, including for multiplexed imaging, the inability to map very low concentrations of targets using F-MRI raises the need to further enhance this platform's capabilities. Here, we employ the principles of CEST-MRI in F-MRI to obtain a 900-fold signal amplification of a biocompatible fluorinated agent, which can be presented in a "multicolor" fashion. Capitalizing on the dynamic interactions in host-guest supramolecular assemblies in an approach termed GEST, we demonstrate that an inhalable fluorinated anesthetic can be used as a single F-probe for the concurrent detection of micromolar levels of two targets, with potential in vivo translatability. Further extending GEST with new designs could expand the applicability of F-MRI to the mapping of targets that have so-far remained non-detectable.
核自旋的微弱热极化限制了 MRI 的灵敏度，即使对于氟-19 等对 MRI 敏感的核也如此。因此，尽管氟是为各种应用开发背景抑制 MRI 的灵感来源，包括用于多重成像，但由于无法使用 F-MRI 对非常低浓度的靶标进行成像，因此需要进一步提高该平台的能力。在这里，我们在 F-MRI 中利用 CEST-MRI 的原理，使生物相容性氟代试剂的信号放大了 900 倍，该试剂可以以“多色”的方式呈现。利用主客体超分子组装中的动态相互作用，我们通过一种称为 GEST 的方法证明，吸入式氟麻醉剂可用作单个 F 探针，用于同时检测两种靶标（浓度为微摩尔级），具有潜在的体内转化能力。通过新设计进一步扩展 GEST，可以将 F-MRI 的适用性扩展到迄今仍无法检测到的靶标的成像。
