Fluorescent Imaging of Lung Lesions During Surgery May Localize Tumors and Improve Precision
More than 80,000 people undergo resection of a pulmonary tumor each year, and currently the only method to determine whether the tumor is malignant is histologic analysis. A new study reported that a targeted molecular contrast agent can be used successfully to render lung adenocarcinomas fluorescent during pulmonary surgery, enabling real-time optical imaging during surgery and the identification of cancer cells. The results are reported by Okusanya et al in The Journal of Thoracic and Cardiovascular Surgery.
“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.
Study Methods
In this proof-of-concept study, 50 patients (aged 25–85 years) with diagnosed adenocarcinoma received 0.1 mg/kg of a fluorescent folate receptor alpha–targeted molecular contrast agent 4 hours before surgery. This agent binds to folate receptor alpha, 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.
Once the chest cavity was opened, the primary lesion was located using traditional methods of visual inspection and manual palpation. The cancer was imaged and photodocumented with a specialized imaging system.
Study Results
In 7 of the 50 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. 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 folate receptor alpha antigens to allow localization of the contrast agent to the tumor. Thus, the folate receptor alpha imaging agent is not useful for all lung adenocarcinomas.
“This technology is safe,” stated Dr. Singhal. “The use of a visible-wavelength fluorophore avoids ionizing radiation and confers no risk to the patient, surgeon, or operating room personnel. In our experience, only one patient had a mild allergic reaction to the contrast agent that was easily managed with diphenhydramine. With miniaturization of imaging devices, this method will be particularly useful in minimally invasive surgery, such as video-assisted thoracoscopic surgery and robotic surgery.”
Dr. Singhal is the corresponding author of The Journal of Thoracic and Cardiovascular Surgery article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
