Synthesis and evaluation of a [18F]BODIPY-labeled caspase-inhibitor

Christian Paul Ortmeyer; Günter Haufe; Katrin Schwegmann; Sven Hermann; Michael Schäfers; Frederik Börgel; Bernhard Wünsch; Stefan Wagner; Verena Hugenberg

doi:10.1016/j.bmc.2017.02.033

Synthesis and evaluation of a [¹⁸F]BODIPY-labeled caspase-inhibitor

Bioorg Med Chem. 2017 Apr 1;25(7):2167-2176. doi: 10.1016/j.bmc.2017.02.033. Epub 2017 Feb 16.

Authors

Christian Paul Ortmeyer¹, Günter Haufe², Katrin Schwegmann³, Sven Hermann³, Michael Schäfers⁴, Frederik Börgel⁵, Bernhard Wünsch⁵, Stefan Wagner⁶, Verena Hugenberg⁷

Affiliations

¹ 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.
² 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.
³ European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, D-48149 Münster, Germany.
⁴ 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.
⁵ Institute for Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstr. 48, D-48149 Münster, Germany.
⁶ Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, D-48149 Münster, Germany.
⁷ Institute for Radiology, Nuclear Medicine and Molecular Imaging, HDZ NRW, Georgstr. 11, D-32545 Bad Oeynhausen, Germany.

PMID: 28284866
DOI: 10.1016/j.bmc.2017.02.033

Abstract

BODIPYs (boron dipyrromethenes) are fluorescent dyes which show high stability and quantum yields. They feature the possibility of selective ¹⁸F-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.

Keywords: (18)F-labeling; BODIPY; Caspase inhibitor; Dual-labeled probe; Molecular Imaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Boron Compounds / chemical synthesis*
Boron Compounds / pharmacokinetics
Boron Compounds / pharmacology*
Chromatography, Liquid
Cycloaddition Reaction
Fluorine Radioisotopes / pharmacokinetics
Fluorine Radioisotopes / pharmacology*
Mice
Mice, Inbred C57BL
Microsomes, Liver / drug effects
Multimodal Imaging
Spectrum Analysis / methods
Tissue Distribution

Substances

4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
Boron Compounds
Fluorine Radioisotopes