title: uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer: proof-of-concept in orthotopic xenograft model.
abstract: OBJECTIVE
  Urokinase-like Plasminogen Activator Receptor (uPAR) is overexpressed in a variety of carcinoma types, and therefore represents an attractive imaging target. The aim of this study was to assess the feasibility of two uPAR-targeted probes for PET and fluorescence tumor imaging in a human xenograft tongue cancer model.
  
  
  RESULTS
  Tumor growth of tongue cancer was monitored by bioluminescence imaging (BLI) and MRI. Either ICG-Glu-Glu-AE105 (fluorescent agent) or 64Cu-DOTA-AE105 (PET agent) was injected systemically, and fluorescence imaging or PET/CT imaging was performed. Tissue was collected for micro-fluorescence imaging and histology. A clear fluorescent signal was detected in the primary tumor with a mean in vivo tumor-to-background ratio of 2.5. Real-time fluorescence-guided tumor resection was possible, and sub-millimeter tumor deposits could be localized. Histological analysis showed co-localization of the fluorescent signal, uPAR expression and tumor deposits. In addition, the feasibility of uPAR-guided robotic cancer surgery was demonstrated. Also, uPAR-PET imaging showed a clear and localized signal in the tongue tumors.
  
  
  CONCLUSIONS
  This study demonstrated the feasibility of combining two uPAR-targeted probes in a preclinical head and neck cancer model. The PET modality provided preoperative non-invasive tumor imaging and the optical modality allowed for real-time fluorescence-guided tumor detection and resection. Clinical translation of this platform seems promising.
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Denmark.|Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Christensen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Karina
authors.initials: K
authors.lastname: Juhl
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Persson
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Birgitte Wittenborg
authors.initials: BW
authors.lastname: Charabi
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Jann
authors.initials: J
authors.lastname: Mortensen
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kiss
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Giedrius
authors.initials: G
authors.lastname: Lelkaitis
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Niclas
authors.initials: N
authors.lastname: Rubek
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D055293:Receptors, Urokinase Plasminogen Activator / Q000032:analysis*; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D025321:Surgery, Computer-Assisted / Q000379:methods*; D014062:Tongue Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; D055293:Receptors, Urokinase Plasminogen Activator
keywords: PET; head and neck cancer; image-guided surgery; tumor margin assessment; uPAR