title: Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent.
abstract: Earlier and more accurate detection of oral squamous cell carcinoma (OSCC) is essential to improve the prognosis of patients and to reduce the morbidity of surgical therapy. Here, we demonstrate that the nuclear enzyme Poly(ADP-ribose)Polymerase 1 (PARP1) is a promising target for optical imaging of OSCC with the fluorescent dye PARPi-FL. In patient-derived OSCC specimens, PARP1 expression was increased 7.8 ± 2.6-fold when compared to normal tissue. Intravenous injection of PARPi-FL allowed for high contrast in vivo imaging of human OSCC models in mice with a surgical fluorescence stereoscope and high-resolution imaging systems. The emitted signal was specific for PARP1 expression and, most importantly, PARPi-FL can be used as a topical imaging agent, spatially resolving the orthotopic tongue tumors in vivo. Collectively, our results suggest that PARP1 imaging with PARPi-FL can enhance the detection of oral cancer, serve as a screening tool and help to guide surgical resections.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kossatz
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Brand
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Gutiontov
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jonathan T C
authors.initials: JT
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Lee
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA.|Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D005456:Fluorescent Dyes; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D061848:Optical Imaging / Q000379:methods; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000302:isolation & purification*; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1