title: Multimodal chelation platform for near-infrared fluorescence/nuclear imaging.
abstract: Dual-labeled compounds containing nuclear and near-infrared fluorescence contrast have the potential to molecularly guide surgical resection of cancer by extending whole-body diagnostic imaging findings into the surgical suite. To simplify the dual labeling process for antibody-based agents, we designed a multimodality chelation (MMC) scaffold which combined a radiometal chelating agent and fluorescent dye into a single moiety. Three dye-derivatized MMC compounds were synthesized and radiolabeled. The IRDye 800CW conjugate, 4, had favorable optical properties and showed rapid clearance in vivo. Using 4, an epithelial cell adhesion molecule (EpCAM) targeting MMC-immunoconjugate was prepared and dual-labeled with (64)Cu. In vitro binding activity was confirmed after MMC conjugation. Multimodal imaging studies showed higher tumor accumulation of (64)Cu-7 compared to nontargeted (64)Cu-4 in a prostate cancer model. Further evaluation in different EpCAM-expressing cell lines is warranted as well as application of the MMC dual labeling approach with other monoclonal antibodies.
authors.affiliation: Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston , Houston, Texas 77030, USA.
authors.forename: Sukhen C
authors.initials: SC
authors.lastname: Ghosh
authors.forename: Pradip
authors.initials: P
authors.lastname: Ghosh
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Wilganowski
authors.forename: Holly
authors.initials: H
authors.lastname: Robinson
authors.forename: Mary A
authors.initials: MA
authors.lastname: Hall
authors.forename: Gabriel
authors.initials: G
authors.lastname: Dickinson
authors.forename: Ken L
authors.initials: KL
authors.lastname: Pinkston
authors.forename: Barrett R
authors.initials: BR
authors.lastname: Harvey
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
authors.forename: Ali
authors.initials: A
authors.lastname: Azhdarinia
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry*; D003952:Diagnostic Imaging / Q000379:methods*; D000071858:Epithelial Cell Adhesion Molecule; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000601:surgery; D011868:Radioisotopes / Q000493:pharmacokinetics
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D002614:Chelating Agents; D000071858:Epithelial Cell Adhesion Molecule; D005456:Fluorescent Dyes; D011868:Radioisotopes