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

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.