Bispidines for dual imaging.

Abstract

The efficient transformation of the hexadentate bispidinol 1 into carbamate derivatives yields functional bispidines enabling convenient functionalization for targeted imaging. The BODIPY-substituted bispidine 3 combines a coordination site for metal ions, such as radioactive (64) Cu(II) , with a fluorescent unit. Product 3 was thoroughly characterized by standard analytical methods, single crystal X-ray 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, whereas Ni(II) and Zn(II) ions do not affect it. It follows that, in imaging applications with the positron emitter (64) Cu(II) , residues of its origin from enriched (64) Ni and the decay products (64) Ni(II) and (64) Zn(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 (64) Cu(II) 3 complex is investigated by transmetalation experiments with Zn(II) and Ni(II) , using fluorescence and radioactivity detection, and the results confirm the high stability of (64) Cu(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.