title: Trifunctional 99mTc based radiopharmaceuticals: metal-mediated conjugation of a peptide with a nucleus targeting intercalator.
abstract: The development of molecular imaging agents with multiple functions has become a major trend in radiopharmaceutical chemistry. We present herein the syntheses of trifunctional compounds, combining an acridine orange (AO) based intercalator with a GRP receptor specific bombesin like peptide (BBN). Metal-mediated conjugation of these two functions via the [2 + 1] approach to the third function, the [M(CO)(3)](+) (M = (99m)Tc, Re) moiety, yielded the final trifunctional molecules. The strongly fluorescent acridine orange, a nuclear targeting agent, has been derivatised with 4-imidazolecarboxylate as a bidentate ligand and bombesin with an isonitrile group as a monodentate ligand. For cell and nuclear uptake studies, [Re(L(1)-BBN)(L(2)-Ical)(CO)(3)] type complexes were synthesized and characterized. For radiopharmaceutical purposes, the (99m)Tc analogues have been prepared in a stepwise synthesis. Fluorescence microscopy studies on PC-3 cells, bearing the BBN receptor, showed high and rapid uptake into the cytoplasm. For the bifunctional molecule, lacking the BBN peptide, no internalization was observed.
authors.affiliation: Institute of Inorganic Chemistry, University of Zürich, Winterthurerstr. 190, 8057, Zürich, Switzerland.
authors.forename: Karel
authors.initials: K
authors.lastname: Zelenka
authors.forename: Lubor
authors.initials: L
authors.lastname: Borsig
authors.forename: Roger
authors.initials: R
authors.lastname: Alberto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D013667:Technetium / Q000737:chemistry*
chemical_list: D008024:Ligands; D010455:Peptides; D019275:Radiopharmaceuticals; D013667:Technetium