title: Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection.
abstract: BACKGROUND
  More than 80,000 people undergo resection of a pulmonary tumor each year, and the only method to determine if the tumor is malignant is histologic analysis. We propose that a targeted molecular contrast agent could bind lung adenocarcinomas, which could be identified using real-time optical imaging at the time of surgery.
  
  
  METHODS
  Fifty patients with a biopsy-proven lung adenocarcinoma were enrolled. Before surgery, patients were systemically administered 0.1 mg/kg of a fluorescent folate receptor alpha (FRα)-targeted molecular contrast agent by intravenous infusion. During surgery, tumors were imaged in situ and ex vivo, after the lung parenchyma was dissected to directly expose the tumor to the imaging system.
  
  
  RESULTS
  Tumors ranged from 0.3 to 7.5 cm (mean: 2.6 cm), and 46 of 50 (92%) lung adenocarcinomas were fluorescent. No false uptake occurred, and in 2 cases, intraoperative imaging revealed tumor metastases (3 mm and 6 mm) that were not recognized preoperatively. Four adenocarcinomas were not fluorescent, and immunohistochemistry showed that these adenocarcinomas did not express FRα. Tumor fluorescence was independent of nodule size, uptake of 2-deoxy-2-((18)F)fluoro-D-glucose, histology, and tumor differentiation. Molecular imaging could identify only 7 of the 50 adenocarcinomas in situ in the patient without bisection. The most important predictor of the success of molecular imaging in locating the tumor in situ was the distance of the nodule from the pleural surface.
  
  
  CONCLUSIONS
  Intraoperative molecular imaging with a targeted contrast agent can identify lung adenocarcinomas, and this technology is currently useful in patients with subpleural tumors, irrespective of size. With further refinements, this tool may prove useful in locating adenocarcinomas that are deeper in the lung parenchyma, in lymph nodes, and at pleural and resection margins.
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Olugbenga T
authors.initials: OT
authors.lastname: Okusanya
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: DeJesus
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Jack X
authors.initials: JX
authors.lastname: Jiang
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Judy
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Ollin G
authors.initials: OG
authors.lastname: Venegas
authors.affiliation: Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.
authors.forename: Charuhas G
authors.initials: CG
authors.lastname: Deshpande
authors.affiliation: Department of Biostatistics & Epidemiology, University of Pennsylvania, Philadelphia, Pa.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Heitjan
authors.affiliation: Departments of Biomedical Engineering and Chemistry, Emory University, Atlanta, Ga.
authors.forename: Shuming
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Ind.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa. Electronic address: sunil.singhal@uphs.upenn.edu.
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging; D016343:Monitoring, Intraoperative; D010865:Pilot Projects; D011013:Pneumonectomy
chemical_list: D005456:Fluorescent Dyes; D016650:Fluorescein-5-isothiocyanate
keywords: Intraoperative imaging; folate imaging; image-guided surgery; lung cancer