Open Accessβ-Diketonate-Iron(III) Complex: A Versatile Fluorine-19 MRI Signal Enhancement Agent
Author(s) -
Chao Wang,
Stephen Adams,
Hongyan Xu,
Wenzhen Zhu,
Eric T. Ahrens
Publication year - 2019
Publication title -
acs applied bio materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.764
H-Index - 17
ISSN - 2576-6422
DOI - 10.1021/acsabm.9b00455
Subject(s) - chelation , relaxometry , chemistry , ferric , fluorine 19 nmr , magnetic resonance imaging , ion , metal ions in aqueous solution , fluorine , materials science , nuclear magnetic resonance , nuclear magnetic resonance spectroscopy , inorganic chemistry , organic chemistry , medicine , physics , spin echo , radiology
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.