title: Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model.
abstract: Complete tumor resection is the most important predictor of patient survival with non-small cell lung cancer. Methods for intraoperative margin assessment after lung cancer excision are lacking. This study evaluated near-infrared (NIR) intraoperative imaging with a folate-targeted molecular contrast agent (OTL0038) for the localization of primary lung adenocarcinomas, lymph node sampling, and margin assessment.
  
  
  
  Ten dogs with lung cancer underwent either video-assisted thoracoscopic surgery or open thoracotomy and tumor excision after an intravenous injection of OTL0038. Lungs were imaged with an NIR imaging device both in vivo and ex vivo. The wound bed was re-imaged for retained fluorescence suspicious for positive tumor margins. The tumor signal-to-background ratio (SBR) was measured in all cases. Next, 3 human patients were enrolled in a proof-of-principle study. Tumor fluorescence was measured both in situ and ex vivo.
  
  
  
  All canine tumors fluoresced in situ (mean Fluoptics SBR, 5.2 [range, 2.7-8.1]; mean Karl Storz SBR 1.9 [range, 1.4-2.6]). In addition, the fluorescence was consistent with tumor margins on pathology. Three positive lymph nodes were discovered with NIR imaging. Also, a positive retained tumor margin was discovered upon NIR imaging of the wound bed. Human pulmonary adenocarcinomas were also fluorescent both in situ and ex vivo (mean SBR, > 2.0).
  
  
  
  NIR imaging can identify lung cancer in a large-animal model. In addition, NIR imaging can discriminate lymph nodes harboring cancer cells and also bring attention to a positive tumor margin. In humans, pulmonary adenocarcinomas fluoresce after the injection of the targeted contrast agent. Cancer 2017;123:1051-60. © 2016 American Cancer Society.
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Center for Precision Surgery, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Keating
authors.affiliation: Center for Precision Surgery, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Runge
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Center for Precision Surgery, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Center for Precision Surgery, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nims
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Center for Precision Surgery, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ollin
authors.initials: O
authors.lastname: Venegas
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Durham
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Gary
authors.initials: G
authors.lastname: Swain
authors.affiliation: Department of Biomedical Engineering, Emory University, Atlanta, Georgia.|Department of Chemistry, Emory University, Atlanta, Georgia.
authors.forename: Shuming
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.affiliation: Center for Precision Surgery, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David E
authors.initials: DE
authors.lastname: Holt
mesh_terms: D000368:Aged; D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D006801:Humans; D007430:Intraoperative Care; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D009367:Neoplasm Staging; D061848:Optical Imaging / Q000379:methods; D059629:Signal-To-Noise Ratio; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D014057:Tomography, X-Ray Computed
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored
keywords: imaging; intraoperative; lung cancer; molecular; near-infrared