title: High-yielding aqueous 18F-labeling of peptides via Al18F chelation.
abstract: The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methylphenylacetic acid (MPAA) backbone, and its ability to form stable Al(18)F chelates were investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF(3). X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55-89%) aqueous (18)F-labeling was achieved in 10-15 min with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al(18)F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging.
authors.affiliation: Immunomedics Inc., 300 American Road, Morris Plains, New Jersey 07950, USA. cdsouza@immunomedics.com
authors.forename: Christopher A
authors.initials: CA
authors.lastname: D'Souza
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Todaro
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000535:Aluminum / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006241:Haptens / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D010455:Peptides / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: C519451:1,4,7-triazacyclononane-1,4-diacetate; D002614:Chelating Agents; D005462:Fluorine Radioisotopes; D006241:Haptens; D006571:Heterocyclic Compounds; D010455:Peptides; D000535:Aluminum