title: Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins.
abstract: OBJECTIVE
  During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection.
  
  
  METHODS
  Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma.
  
  
  RESULTS
  The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (p < 0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5.
  
  
  CONCLUSIONS
  Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Keating
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Olugbenga T
authors.initials: OT
authors.lastname: Okusanya
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: De Jesus
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Judy
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Charuhas
authors.initials: C
authors.lastname: Deshpande
authors.affiliation: Departments of Biomedical Engineering and Chemistry, Emory University, Atlanta, GA, USA.
authors.forename: Shuming
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Low
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania and Philadelphia VA Medical Center, Philadelphia, PA, USA. sunil.singhal@uphs.upenn.edu.|Division of Thoracic Surgery, University of Pennsylvania School of Medicine, 6 White Building, 3400 Spruce Street, Philadelphia, PA, 19104, USA. sunil.singhal@uphs.upenn.edu.
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism / Q000493:pharmacokinetics; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D007430:Intraoperative Care; D008168:Lung / Q000473:pathology / Q000601:surgery; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery*; D000072662:Margins of Excision; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D018365:Neoplasm, Residual / Q000000981:diagnostic imaging* / Q000473:pathology*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored
keywords: Folate receptor alpha; Lung cancer; Molecular imaging; Surgical oncology; Thoracic surgery