Wang Chao, Adams Stephen R, Xu Hongyan, Zhu Wenlian, Ahrens Eric T
Department of Radiology, University of California, San Diego, La Jolla, California 92093, United States.
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, United States.
ACS Appl Bio Mater. 2019 Sep 16;2(9):3836-3842. doi: 10.1021/acsabm.9b00455. Epub 2019 Aug 13.
Fluorine-19 magnetic resonance imaging (MRI) has gained considerable momentum as a promising imaging modality for in vivo tracking of cellular therapies and as a diagnostic for inflammatory disease. To further the utility of this technique, we increase imaging probe sensitivity by merging paramagnetic metal chelates with aqueous perfluorocarbon (PFC) nanoemulsions. We prepared a highly fluorinated ferric tris(-diketonate) chelate (MW = 1265.2 g/mol) at gram scale. This iron chelate is soluble in multiple PFC oils used for MRI and readily reduces the F longitudinal relaxation time ( ) to <100 ms with modest line broadening and displays superior properties for F MRI applications. The sensitivity enhancement by Fe(III) laden PFC nanoemulsion was confirmed in MRI phantom studies, where reduced speeds data acquisition thereby increasing the F image sensitivity per time via signal averaging. Additionally, F relaxivity of nanoemulsions incorporating other metal ions, including Gd, Er, Ho, Dy, Mn, Cr, and Ni, were evaluated. High-moment lanthanide ions, such as Gd(III), display severe line broadening, but other ions [e.g., Ho(III)] induce pseudocontact chemical shifts (up to 0.5 ppm) of F in nanoemulsion, which makes them potentially useful for multichromatic F imaging. Formulated nanoemulsions have a shelf life >200 days. Free -diketonate or its iron complex in formed PFC nanoemulsion did not induce cytotoxicity in intracellularly labeled macrophages. Overall, ferric tris(-diketonate) chelate provides a scalable approach for boosting sensitivity of PFC-based F MRI probes. More generally, it can functionalize PFC oil, whose chemical modification remains challenging.
氟-19磁共振成像（MRI）作为一种用于细胞治疗体内追踪的有前景的成像方式以及炎症性疾病的诊断方法，已获得了相当大的发展势头。为了进一步提高该技术的实用性，我们通过将顺磁性金属螯合物与水性全氟碳（PFC）纳米乳剂合并来提高成像探针的灵敏度。我们以克级规模制备了一种高度氟化的三（二酮）铁螯合物（分子量 = 1265.2 g/mol）。这种铁螯合物可溶于多种用于MRI的PFC油中，并能在适度的线宽展宽情况下将F纵向弛豫时间（ ）降低至<100 ms，且在F MRI应用中表现出优异的性能。在MRI体模研究中证实了负载Fe(III)的PFC纳米乳剂提高了灵敏度，其中降低的 加快了数据采集速度，从而通过信号平均提高了每次的F图像灵敏度。此外，还评估了包含其他金属离子（包括Gd、Er、Ho、Dy、Mn、Cr和Ni）的纳米乳剂的F弛豫率。高磁矩镧系离子，如Gd(III)，表现出严重的线宽展宽，但其他离子[例如Ho(III)]会在纳米乳剂中诱导F的赝接触化学位移（高达0.5 ppm），这使得它们在多色F成像中具有潜在用途。配制的纳米乳剂保质期>200天。形成的PFC纳米乳剂中的游离二酮或其铁络合物在细胞内标记的巨噬细胞中未诱导细胞毒性。总体而言，三（二酮）铁螯合物为提高基于PFC的F MRI探针的灵敏度提供了一种可扩展的方法。更一般地说，它可以使PFC油功能化，而PFC油的化学修饰仍然具有挑战性。
