title: 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.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, PF 510119, 01314 Dresden (Germany), Fax: (+49) 351-2603232. h.stephan@hzdr.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Stephan
authors.forename: Martin
authors.initials: M
authors.lastname: Walther
authors.forename: Silke
authors.initials: S
authors.lastname: Fähnemann
authors.forename: Paola
authors.initials: P
authors.lastname: Ceroni
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Molloy
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bergamini
authors.forename: Fabian
authors.initials: F
authors.lastname: Heisig
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Werner
authors.initials: W
authors.lastname: Kraus
authors.forename: Peter
authors.initials: P
authors.lastname: Comba
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003952:Diagnostic Imaging / Q000379:methods*; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D008024:Ligands; D049408:Luminescent Agents / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002614:Chelating Agents; D056831:Coordination Complexes; D028581:Lanthanoid Series Elements; D008024:Ligands; D049408:Luminescent Agents; C495809:bispidine
keywords: bispidines; chelates; imaging agents; lanthanides; radiolabeling