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Author Notes:

Corresponding Author: Sunil Singhal, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104, sunil.singhal@uphs.upenn.edu

We would like to thank Dr. Joel D. Cooper, Professor of Surgery at the University of Pennsylvania School of Medicine, for his invaluable input and guidance in this body of work.

Disclosures: SN is a consultant for SpectroPath, Inc., a startup company to develop advanced instrumentation and nanoparticle contrast agents. PSL is a consultant and stake holder in OnTarget Laboratories LLC.

Subjects:

Research Funding:

The project described was partially supported by Award Number I011CX001189 (SS, CD) from the Biomedical Laboratory Research &Development Service of the VA Office of Research and Development and by the CHEST Foundation One Breath Clinical Research Award (SS).

Keywords:

  • Intraoperative imaging
  • folate imaging
  • image-guided surgery
  • lung cancer
  • Adenocarcinoma
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Humans
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Molecular Imaging
  • Monitoring, Intraoperative
  • Pilot Projects
  • Pneumonectomy

Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection

Tools:

Journal Title:

Journal of Thoracic and Cardiovascular Surgery

Volume:

Volume 150, Number 1

Publisher:

, Pages 28-35e1

Type of Work:

Article | Post-print: After Peer Review

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-(18F)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.

Copyright information:

© 2015 The American Association for Thoracic Surgery.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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