Work

β-Diketonate-Iron(III) Complex: A Versatile Fluorine-19 MRI Signal Enhancement Agent

Year: 2019

Type: article

Abstract: 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(β-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 19 F longitudinal relaxation time ( T 1 ) to <100 ms with modest line broadening and displays superior properties for 19 F MRI applications. The sensitivity enhancement by Fe(III) laden PFC nanoemulsion was confirmed in MRI phantom studies, where reduced T 1 speeds data acquisition thereby increasing the 19 F image sensitivity per time via signal averaging. Additionally, 19 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 19 F in nanoemulsion, which makes them potentially useful for multichromatic 19 F imaging. Formulated nanoemulsions have a shelf life >200 days. Free β-diketonate or its iron complex in formed PFC nanoemulsion did not induce cytotoxicity in intracellularly labeled macrophages. Overall, ferric tris(β-diketonate) chelate provides a scalable approach for boosting sensitivity of PFC-based 19 F MRI probes. More generally, it can functionalize PFC oil, whose chemical modification remains challenging.

Source: ACS Applied Bio Materials

DOI: 10.1021/acsabm.9b00455

Authors: Chao Wang, Stephen R. Adams, Hongyan Xu, Wenlian Zhu, Eric T. Ahrens

Institution: University of California San Diego

Language: English

Topic: Lanthanide and Transition Metal Complexes

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funders: California Institute for Regenerative Medicine, National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering