Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection

Olugbenga T. Okusanya, Elizabeth M. Dejesus, Jack X. Jiang, Ryan P. Judy, Ollin G. Venegas, Charuhas G. Deshpande, Daniel F. Heitjan, Shuming Nie, Philip S. Low, Sunil Singhal

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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.

Original languageEnglish (US)
Pages (from-to)28-35e1
JournalJournal of Thoracic and Cardiovascular Surgery
Volume150
Issue number1
DOIs
StatePublished - Jan 1 2015

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Molecular Imaging
Lung
Neoplasms
Folate Receptor 1
Contrast Media
Adenocarcinoma
Adenocarcinoma of lung
Optical Imaging
Fluorodeoxyglucose F18
Intravenous Infusions
Histology
Fluorescence
Lymph Nodes
Immunohistochemistry
Neoplasm Metastasis
Technology
Biopsy

Keywords

  • folate imaging
  • image-guided surgery
  • Key Words Intraoperative imaging
  • lung cancer

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Okusanya, O. T., Dejesus, E. M., Jiang, J. X., Judy, R. P., Venegas, O. G., Deshpande, C. G., ... Singhal, S. (2015). Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection. Journal of Thoracic and Cardiovascular Surgery, 150(1), 28-35e1. https://doi.org/10.1016/j.jtcvs.2015.05.014

Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection. / Okusanya, Olugbenga T.; Dejesus, Elizabeth M.; Jiang, Jack X.; Judy, Ryan P.; Venegas, Ollin G.; Deshpande, Charuhas G.; Heitjan, Daniel F.; Nie, Shuming; Low, Philip S.; Singhal, Sunil.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 150, No. 1, 01.01.2015, p. 28-35e1.

Research output: Contribution to journalArticle

Okusanya, OT, Dejesus, EM, Jiang, JX, Judy, RP, Venegas, OG, Deshpande, CG, Heitjan, DF, Nie, S, Low, PS & Singhal, S 2015, 'Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection', Journal of Thoracic and Cardiovascular Surgery, vol. 150, no. 1, pp. 28-35e1. https://doi.org/10.1016/j.jtcvs.2015.05.014
Okusanya, Olugbenga T. ; Dejesus, Elizabeth M. ; Jiang, Jack X. ; Judy, Ryan P. ; Venegas, Ollin G. ; Deshpande, Charuhas G. ; Heitjan, Daniel F. ; Nie, Shuming ; Low, Philip S. ; Singhal, Sunil. / Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection. In: Journal of Thoracic and Cardiovascular Surgery. 2015 ; Vol. 150, No. 1. pp. 28-35e1.
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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.",
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AU - Okusanya, Olugbenga T.

AU - Dejesus, Elizabeth M.

AU - Jiang, Jack X.

AU - Judy, Ryan P.

AU - Venegas, Ollin G.

AU - Deshpande, Charuhas G.

AU - Heitjan, Daniel F.

AU - Nie, Shuming

AU - Low, Philip S.

AU - Singhal, Sunil

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N2 - 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.

AB - 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.

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