title: Affibody-targeted fluorogen activating protein for in vivo tumor imaging.
abstract: Molecular imaging using near-infrared (NIR) fluorescence is useful for intraoperative imaging and real-time margin identification. Directly conjugated IR dyes possess useful properties for in vivo imaging, but conjugation often substantially alters the circulation dynamics of targeting moieties. We developed and characterized a new tumor-targeting probe, affiFAP, which consists of a protein that specifically binds EGFR (affibody) and a fluorogen activating protein (FAP). This compact molecular recognition reagent can reversibly bind and activate fluorescence of otherwise nonfluorescent dyes and allows tumor visualization with low nonspecific tissue staining. We demonstrate molecular pre-targeting of affiFAPs and subsequent systemic or topical application of fluorogenic dye to achieve high contrast, fast clearance, and good tissue penetration that may be used in clinical settings to molecularly define tumor margins.
authors.affiliation: The Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA. bruchez@cmu.edu and The Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Byron
authors.initials: B
authors.lastname: Ballou
authors.affiliation: The Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Brigitte F
authors.initials: BF
authors.lastname: Schmidt
authors.affiliation: The Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Sue
authors.initials: S
authors.lastname: Andreko
authors.affiliation: Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Claudette M
authors.initials: CM
authors.lastname: St Croix
authors.affiliation: Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.affiliation: The Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA. bruchez@cmu.edu and The Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213, USA and The Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Marcel P
authors.identifier: http://orcid.org/0000-0002-7370-4848
authors.initials: MP
authors.lastname: Bruchez
mesh_terms: D000818:Animals; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D007259:Infrared Rays; D051379:Mice; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D061848:Optical Imaging; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D057127:Single-Chain Antibodies / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D043562:Receptors, G-Protein-Coupled; D057127:Single-Chain Antibodies