title: Paramagnetic fluorinated nanoemulsions for sensitive cellular fluorine-19 magnetic resonance imaging.
abstract: Fluorine-19 magnetic resonance imaging ((19)F MRI) probes enable quantitative in vivo detection of cell therapies and inflammatory cells. Here, we describe the formulation of perfluorocarbon-based nanoemulsions with improved sensitivity for cellular MRI. Reduction of the (19)F spin-lattice relaxation time (T1) enables rapid imaging and an improved signal-to-noise ratio, thereby improving cell detection sensitivity. We synthesized metal-binding β-diketones conjugated to linear perfluoropolyether (PFPE), formulated these fluorinated ligands as aqueous nanoemulsions, and then metallated them with various transition and lanthanide ions in the fluorous phase. Iron(III) tris-β-diketonate ('FETRIS') nanoemulsions with PFPE have low cytotoxicity (<20%) and superior MRI properties. Moreover, the (19)F T1 can readily be reduced by an order of magnitude and tuned by stoichiometric modulation of the iron concentration. The resulting (19)F MRI detection sensitivity is enhanced by three- to fivefold over previously used tracers at 11.7 T, and is predicted to increase by at least eightfold at the clinical field strength of 3 T.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Kislukhin
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Adams
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Kazim H
authors.initials: KH
authors.lastname: Narsinh
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.|Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.|Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Tsien
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Ahrens
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry*; D066235:Fluorine-19 Magnetic Resonance Imaging / Q000379:methods*; D005466:Fluorocarbons / Q000737:chemistry*; D051379:Mice; D051381:Rats; D012680:Sensitivity and Specificity
chemical_list: D005290:Ferric Compounds; D005466:Fluorocarbons