title: Fast 18F labeling of a near-infrared fluorophore enables positron emission tomography and optical imaging of sentinel lymph nodes.
abstract: We combine a novel boronate trap for F(-) with a near-infrared fluorophore into a single molecule. Attachment to targeting ligands enables localization by positron emission tomography (PET) and near-infrared fluorescence (NIRF). Our first application of this generic tag is to label Lymphoseek (tilmanocept), an agent designed for receptor-specific sentinel lymph node (SLN) mapping. The new conjugate incorporates (18)F(-) in a single, aqueous step, targets mouse SLN rapidly (1 h) with reduced distal lymph node accumulation, permits PET or scintigraphic imaging of SLN, and enables NIRF-guided excision and histological verification even after (18)F decay. This embodiment is superior to current SLN mapping agents such as nontargeted [(99m)Tc]sulfur colloids and Isosulfan Blue, as well as the phase III targeted ligand [(99m)Tc]SPECT Lymphoseek counterpart, species that are visible by SPECT or visible absorbance separately. Facile incorporation of (18)F into a NIRF probe should promote many synergistic PET and NIRF combinations.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Ting
authors.forename: Todd A
authors.initials: TA
authors.lastname: Aguilera
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Crisp
authors.forename: David J
authors.initials: DJ
authors.lastname: Hall
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
authors.forename: David R
authors.initials: DR
authors.lastname: Vera
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Tsien
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D007259:Infrared Rays; D007553:Isotope Labeling / Q000379:methods*; D007700:Kinetics; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D008351:Mannans / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D055620:Optical Phenomena; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D021701:Sentinel Lymph Node Biopsy; D016284:Technetium Tc 99m Pentetate / Q000031:analogs & derivatives; D014057:Tomography, X-Ray Computed
chemical_list: D001897:Boronic Acids; D003911:Dextrans; D005456:Fluorescent Dyes; D005462:Fluorine Radioisotopes; D008351:Mannans; D015609:Organotechnetium Compounds; C431884:technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate