Bispidines for dual imaging

The efficient transformation of the hexadentate bispidinol 1 into carbamate derivatives yields functional bispidines for the convenient functionalization for targeted imaging. The BODIPY-substituted bispidine 3 combines the coordination site for metal ions (e.g., radioactive ⁶⁴Cu^II) with a fluorescent unit. Product 3 was thoroughly characterized by standard analytical methods, single crystal diffraction, radiolabeling and photophysical analysis. The luminescence of ligand 3 was found to be strongly dependent on metal ion coordination: Cu^II quenches the BODIPY fluorescence, while Ni^II and Zn^II ions do not affect it. It follows that, in imaging applications with the positron emitter ⁶⁴Cu^II, residues of its origin from enriched ⁶⁴Ni and the decay products ⁶⁴Ni^II and ⁶⁴Zn^II, efficiently restore the fluorescence of the ligand. This allows for monitoring of the emitted radiation as well as the fluorescence signal. The stability of the ⁶⁴Cu^II-3 complex was investigated by transmetalation experiments with Zn^II and Ni^II, using fluorescence and radioactivity detection and the results confirm the high stability of ⁶⁴Cu^II-3. In addition, metal complexes of ligand 3 with the lanthanide ions Tb^III, Eu^III and Nd^III are shown to exhibit emission of the BODIPY ligand and the lanthanide ion, thus enabling dual emission detection.