title: Beyond the margins: real-time detection of cancer using targeted fluorophores.
abstract: Over the past two decades, synergistic innovations in imaging technology have resulted in a revolution in which a range of biomedical applications are now benefiting from fluorescence imaging. Specifically, advances in fluorophore chemistry and imaging hardware, and the identification of targetable biomarkers have now positioned intraoperative fluorescence as a highly specific real-time detection modality for surgeons in oncology. In particular, the deeper tissue penetration and limited autofluorescence of near-infrared (NIR) fluorescence imaging improves the translational potential of this modality over visible-light fluorescence imaging. Rapid developments in fluorophores with improved characteristics, detection instrumentation, and targeting strategies led to the clinical testing in the early 2010s of the first targeted NIR fluorophores for intraoperative cancer detection. The foundations for the advances that underline this technology continue to be nurtured by the multidisciplinary collaboration of chemists, biologists, engineers, and clinicians. In this Review, we highlight the latest developments in NIR fluorophores, cancer-targeting strategies, and detection instrumentation for intraoperative cancer detection, and consider the unique challenges associated with their effective application in clinical settings.
authors.affiliation: Department of Radiology, University of Wisconsin-Madison (UW-Madison), 600 Highland Avenue, Madison, Wisconsin 53792, USA.|Department of Neurological Surgery, UW-Madison, 600 Highland Avenue, Madison, Wisconsin 53792, USA.
authors.forename: Ray R
authors.initials: RR
authors.lastname: Zhang
authors.affiliation: Medical Engineering, Morgridge Institute for Research, 330 North Orchard Street, Madison, Wisconsin 53715, USA.|Laboratory for Optical and Computational Instrumentation, 1675 Observatory Drive, Madison Wisconsin 53706, USA.|Department of Medical Physics, UW-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Schroeder
authors.affiliation: Department of Medical Physics, UW-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Grudzinski
authors.affiliation: Department of Otolaryngology, Stanford Cancer Center, 875 Blake Wilbur Drive, Stanford, California 94305, USA.
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
authors.affiliation: Department of Otolaryngology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Warram
authors.affiliation: Department of Radiology, University of Wisconsin-Madison (UW-Madison), 600 Highland Avenue, Madison, Wisconsin 53792, USA.
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Pinchuk
authors.affiliation: Medical Engineering, Morgridge Institute for Research, 330 North Orchard Street, Madison, Wisconsin 53715, USA.|Laboratory for Optical and Computational Instrumentation, 1675 Observatory Drive, Madison Wisconsin 53706, USA.|Department of Medical Physics, UW-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.|Carbone Cancer Center, UW-Madison, 600 Highland Avenue Madison, Wisconsin 53792, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Eliceiri
authors.affiliation: Department of Neurological Surgery, UW-Madison, 600 Highland Avenue, Madison, Wisconsin 53792, USA.|Carbone Cancer Center, UW-Madison, 600 Highland Avenue Madison, Wisconsin 53792, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Kuo
authors.affiliation: Department of Radiology, University of Wisconsin-Madison (UW-Madison), 600 Highland Avenue, Madison, Wisconsin 53792, USA.|Department of Medical Physics, UW-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.|Carbone Cancer Center, UW-Madison, 600 Highland Avenue Madison, Wisconsin 53792, USA.
authors.forename: Jamey P
authors.initials: JP
authors.lastname: Weichert
mesh_terms: D055808:Drug Discovery / Q000379:methods / Q000639:trends; D005456:Fluorescent Dyes; D006801:Humans; D007208:Indocyanine Green; D007430:Intraoperative Care; D007982:Levulinic Acids; D008751:Methylene Blue; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D000622:Aminolevulinic Acid
chemical_list: D005456:Fluorescent Dyes; D007208:Indocyanine Green; D007982:Levulinic Acids; D008751:Methylene Blue; D000622:Aminolevulinic Acid