Department of Chemistry, University of Minnesota - Twin Cities, 207 Pleasant St. SE, Minneapolis, MN, 55455, USA.
Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota - Twin Cities, 2021 6thSt. SE, Minneapolis, MN, 55455, USA.
Angew Chem Int Ed Engl. 2017 Jun 1;56(23):6440-6444. doi: 10.1002/anie.201700426. Epub 2017 May 4.
F MRI is valuable for in vivo imaging due to the only trace amounts of fluorine in biological systems. Because of the low sensitivity of MRI however, designing new fluorochemicals remains a significant challenge for achieving sufficient F signal. Here, we describe a new class of high-signal, water-soluble fluorochemicals as F MRI imaging agents. A polyamide backbone is used for tuning the proteolytic stability to avoid retention within the body, which is a limitation of current state-of-the-art perfluorochemicals. We show that unstructured peptides containing alternating N-ϵ-trifluoroacetyllysine and lysine provide a degenerate F NMR signal. F MRI phantom images provide sufficient contrast at micromolar concentrations, showing promise for eventual clinical applications. Finally, the degenerate high signal characteristics were retained when conjugated to a large protein, indicating potential for in vivo targeting applications, including molecular imaging and cell tracking.
由于生物系统中氟的含量极少，因此 fMRI 在体内成像是很有价值的。然而，由于 MRI 的灵敏度较低，因此设计新的氟化学物质仍然是实现足够 F 信号的重大挑战。在这里，我们描述了一类新的高信号、水溶性氟化学物质，它们可用作 F MRI 成像剂。采用聚酰胺骨架来调整蛋白水解稳定性，以避免在体内保留，这是当前最先进的全氟化学物质的一个局限性。我们表明，含有交替的 N-ε-三氟乙酰赖氨酸和赖氨酸的无规多肽提供了退化的 F NMR 信号。F MRI 体模图像在微摩尔浓度下提供了足够的对比度，显示出最终临床应用的前景。最后，当与大蛋白结合时，退化的高信号特性得以保留，表明有可能用于体内靶向应用，包括分子成像和细胞跟踪。
