title: Small BODIPY Probes for Combined Dual (19) F MRI and Fluorescence Imaging.
abstract: The combination of the two complementary imaging modalities (19) F magnetic resonance imaging (MRI) and fluorescence imaging (FLI) possesses high potential for biological and medical applications. Herein we report the first design, synthesis, dual detection validation, and cytotoxic testing of four promising BODIPY dyes for dual (19) F MRI-fluorescence detection. Using straightforward Steglich reactions, small fluorinated alcohols were easily covalently tethered to a BODIPY dye in high yields, leaving its fluorescence properties unaffected. The synthesized compounds were analyzed with various techniques to demonstrate their potential utility in dual imaging. As expected, the chemically and magnetically equivalent trifluoromethyl groups of the agents exhibited a single NMR signal. The determined longitudinal relaxation times T1 and the transverse relaxation times T2 , both in the lower second range, enabled the imaging of four compounds in vitro. The most auspicious dual (19) F MRI-fluorescence agent was also successfully imaged in a mouse post-mortem within a 9.4 T small-animal tomograph. Toxicological assays with human cells (primary HUVEC and HepG2 cell line) also indicated the possibility for animal testing.
authors.affiliation: Department of Chemistry, Biophysical Chemistry, Saarland University, Campus, 66123, Saarbrücken, Germany.
authors.forename: Anh Minh
authors.initials: AM
authors.lastname: Huynh
authors.affiliation: Clinic of Diagnostic and Interventional Radiology, Saarland University Medical Center, 66424, Homburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller
authors.affiliation: Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123, Saarbrücken, Germany.
authors.forename: Sonja M
authors.identifier: 0000-0002-8591-851X
authors.initials: SM
authors.lastname: Kessler
authors.affiliation: Department of Chemistry, Biophysical Chemistry, Saarland University, Campus, 66123, Saarbrücken, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Henrikus
authors.affiliation: Department of Chemistry, Biophysical Chemistry, Saarland University, Campus, 66123, Saarbrücken, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hoffmann
authors.affiliation: Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123, Saarbrücken, Germany.
authors.forename: Alexandra K
authors.identifier: 0000-0002-7224-9900
authors.initials: AK
authors.lastname: Kiemer
authors.affiliation: Clinic of Diagnostic and Interventional Radiology, Saarland University Medical Center, 66424, Homburg, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Bücker
authors.affiliation: Department of Chemistry, Biophysical Chemistry, Saarland University, Campus, 66123, Saarbrücken, Germany. g.jung@mx.uni-saarland.de.
authors.forename: Gregor
authors.initials: G
authors.lastname: Jung
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D005462:Fluorine Radioisotopes; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D013050:Spectrometry, Fluorescence
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes; D005462:Fluorine Radioisotopes
keywords: fluorescence; imaging agents; radiopharmaceuticals; toxicology