FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Injecting patients with a molecular contrast agent before lung cancer surgery and then using fluorescent imaging during the operation proved safe and somewhat effective at finding lung adenocarcinomas and discovering tumor metastases in a pilot clinical trial of 50 patients.
Investigators from the University of Pennsylvania, Philadelphia, and Emory (Atlanta) and Purdue (West Lafayette, Ind.) universities reported their findings online in the Journal of Thoracic and Cardiovascular Surgery (2015 [ doi:10.1016/j.jtcvs.2015.05.014 ]).
“We believe the most important finding in this study was the ability to systemically inject our contrast agent into patients prior to surgery and have 92% of the lung adenocarcinomas fluoresce in the operating room,” Dr. Olugbenga Okusanya of the University of Pennsylvania, Philadelphia, and his colleagues said. Their approach overcomes some of the limitations of other contrast agents for imaging of lung cancer.
The approach involves intravenous administration of 0.1 mg/kg of a fluorescent folate receptor-alpha (FR-alpha)–targeted molecule contrast agent 4 hours before surgery. The specific agent they used is a synthetic conjugate between folate and fluorescein isothiocyanate that binds to serum proteins.
They set out to determine if an optical-targeted molecular contrast agent to FR-alpha could bind lung adenocarcinoma and then if real-time optical imaging, either in situ or ex vivo during surgery, would show the lesions. The 50 study subjects all had biopsy-confirmed lung adenocarcinoma. In the OR, the researchers used a gantry-mounted fluorescent imaging system to capture images of the tumors.
With the operating room lights switched off, imaging of the cancer was captured by fluorescence and white light in situ. The lung was deflated during imaging to expose as much of the lung surface to the imaging as possible. The in situ optical imaging required on average eight minutes to perform. Only seven tumors (14%) appeared fluorescent in situ before they were excised. Computed tomography (CT) before surgery showed that all seven of these tumors were below the pleural surface and within 1.2 cm of the lung surface.
Among the other 43 tumors, 39 exhibited uniform fluorescence once the surgical team exposed their surfaces while 4 – all invasive adenocarcinomas – did not. Final pathology confirmed that all 50 tumors were cancerous.
“With further refinements, this tool may prove useful in locating adenocarcinomas deeper in the lung parenchyma, lymph nodes and at pleural and resection margins,” Dr. Okusanya and his coauthors said.
The investigators noted that one advantage of this imaging strategy is that it can locate tumors of varying sizes, subtypes and metabolic activity with tumor-to-background ratios “not markedly different” among them. “This finding demonstrates that intraoperative molecular imaging may be potentially broadly applicable to all FR-alpha lung tumors,” they said.
Other advantages is that wavelength fluorophore poses no radiation exposure and that surgeons readily understand optical imaging “with no need for special training to interpret or process the data.” They did acknowledge that a significant drawback of the molecular contrast agent was its lack of penetration into the lung parenchyma.
“New molecular tools are emerging to identify lung adenocarcinomas during pulmonary resection,” Dr. Okusanya and colleagues said. “This technology will permit precise visualization of tumor margins, localization of small malignant ground-glass opacities, and accurate selection of lymph nodes with metastatic cancer cells. With miniaturization of imaging devices, this method will be particularly useful in minimally invasive surgery.”
The pilot clinical trial was partially supported by grant from the Biomedical Laboratory Research & Development Service of the Veterans Affairs Office of Research and Development and by the CHEST Foundation One Breath Clinical Research Award (SS).
Dr. Shuming Nie is a coauthor and a consultant for Spectropath, a start-up company that is developing advanced instrumentation and nanoparticle contrast agents. Dr. Philip S. Low is a coauthor and a consultant and stakeholder in OnTarget Laboratories. None of the other coauthors had any relationships to disclose.
