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

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.