title: Synthesis and evaluation of a [18F]BODIPY-labeled caspase-inhibitor.
abstract: BODIPYs (boron dipyrromethenes) are fluorescent dyes which show high stability and quantum yields. They feature the possibility of selective18F-fluorination at the boron-core. Attached to a bioactive molecule and labeled with [18F]fluorine, the resulting compounds are promising tracers for multimodal imaging in vivo and can be used for PET and fluorescence imaging. A BODIPY containing a phenyl and a hydroxy substituent on boron was synthesized and characterized. Fluorinated and hydroxy substituted dyes were coupled to an isatin-based caspase inhibitor via cycloaddition and the resulting compounds were evaluated in vitro in caspase inhibition assays. The metabolic stability and the formed metabolites were investigated by incubation with mouse liver microsomes and LC-MS analysis. Subsequently the fluorophores were labeled with [18F]fluorine and an in vivo biodistribution study using dynamic PET was performed.
authors.affiliation: Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany; Organic Chemistry Institute, University of Münster, Corrensstr. 40, D-48149 Münster, Germany.
authors.forename: Christian Paul
authors.initials: CP
authors.lastname: Ortmeyer
authors.affiliation: Organic Chemistry Institute, University of Münster, Corrensstr. 40, D-48149 Münster, Germany; Cells-in-Motion Cluster of Excellence, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany. Electronic address: jfc@uni-muenster.de.
authors.forename: Günter
authors.initials: G
authors.lastname: Haufe
authors.affiliation: European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwegmann
authors.affiliation: European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.affiliation: Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany; Cells-in-Motion Cluster of Excellence, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany; European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: Institute for Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstr. 48, D-48149 Münster, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Börgel
authors.affiliation: Institute for Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstr. 48, D-48149 Münster, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wünsch
authors.affiliation: Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Institute for Radiology, Nuclear Medicine and Molecular Imaging, HDZ NRW, Georgstr. 11, D-32545 Bad Oeynhausen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Hugenberg
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002853:Chromatography, Liquid; D061565:Cycloaddition Reaction; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects; D064847:Multimodal Imaging; D013057:Spectrum Analysis / Q000379:methods; D014018:Tissue Distribution
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005462:Fluorine Radioisotopes
keywords: (18)F-labeling; BODIPY; Caspase inhibitor; Dual-labeled probe; Molecular Imaging