Targeted molecular contrast agent may improve visualization of lung tumor margins

New molecular tools are emerging to identify lung adenocarcinomas during pulmonary resection. The results of a proof-of-concept study suggest that fluorescent imaging of lung cancer during surgery using targeted molecular agents may soon be a reality. The findings were published in The Journal of Thoracic and Cardiovascular Surgery (2015; doi:10.1016/j.jtcvs.2015.05.014).

While the methodology still needs refinement, the technique holds the possibility of precise visualization of tumor margins, detection of other tumors or metastases, localization of small malignant ground glass opacities, and accurate identification of lymph nodes containing metastatic cancer cells.

More than 80,000 people undergo resection of a pulmonary tumor each year, and currently the only method to determine if the tumor is malignant is histologic analysis. The new study uses a targeted molecular contrast agent that causes lung adenocarcinomas to fluoresce during pulmonary surgery. This enables real-time optical imaging during surgery and the identification of cancer cells.

"This approach may allow surgeons to perform resections with confidence that the entire tumor burden has been eliminated. In the future, with improved devices and molecular contrast agents, this approach may reduce the local recurrence rate and improve intraoperative identification of metastatic cancer cells," explained lead investigator Sunil Singhal, MD, of the Department of Surgery, University of Pennsylvania Perelman School of Medicine in Philadelphia.

In this proof-of-concept study, 50 patients (age 25 to 85 years) with diagnosed adenocarcinoma received 0.1 mg/kg of a fluorescent folate receptor alpha (FRα)-targeted molecular contrast agent 4 hours before surgery. This agent binds to FRα, a protein found on the surface of most lung adenocarcinoma cells. This resulted in fluorescence of 92% of pulmonary adenocarcinomas, allowing surgeons to visually identify tumor cells during surgery.

Upon opening the chest cavity, the primary lesion was located using traditional methods of visual inspection and manual palpation. The cancer was imaged and photo-documented with a specialized imaging system and the FloCam system that their laboratory developed.

In seven cases (14%), the tumor could easily be identified by its fluorescence. The tumors ranged in size from 1.1 to 8.0 cm, but size did not influence fluorescence. All of these tumors were within 1.2 cm of the lung surface.

Of the remaining 43 tumors, 39 appeared fluorescent after the overlying tissue was opened and the tumor exposed. The fluorescence was uniform across the tumor's surface, and the demarcation between tumor and normal surrounding tissue was clearly visible. On average, the optical imaging was quick, ranging from 5 to 15 minutes.

The technique proved to be particularly helpful in two cases. In a 50-year old man thought to have a 2.1-cm primary lung adenocarcinoma in the right upper pulmonary lobe, molecular imaging of the excised lobe identified a second pulmonary nodule that was fluorescent, leading to restaging of the patient. In another patient, who was thought to have no evidence of metastatic disease, molecular imaging showed evidence of cancer elsewhere.

Four tumors (8%) did not exhibit fluorescence, and further analysis showed that these tumors did not express FRα antigens to allow localization of the contrast agent to the tumor. Thus, the FRα imaging agent is not useful for all lung adenocarcinomas.

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