Researchers at the University of Pennsylvania's Perelman School of Medicine (Philadelphia, PA) used real-time fluorescence imaging during surgery to identify lung cancer cells. By using a targeted molecular contrast agent, lung adenocarcinomas fluoresced during pulmonary surgery.
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"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," explains lead investigator Sunil Singhal, MD, of the Perelman School of Medicine's Department of Surgery.
In the researchers' proof-of-concept study, 50 patients (ages 25-85 years) with diagnosed adenocarcinoma received 0.1 mg/kg of a fluorescent folate receptor alpha (FRα)-targeted molecular contrast agent (On Target Laboratories) four hours before surgery. This agent binds to folate receptor α, 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 photodocumented with a fluorescence imaging system (Quest Medical Imaging's Artemis fluorescence imaging system) and the FloCam system developed in their laboratory.
|Intraoperative fluorescence imaging detects a lung adenocarcinoma during a pulmonary resection. (Credit: The Journal of Thoracic and Cardiovascular Surgery)|
In seven 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 five 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 re-staging 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.
"This technology is safe," states 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 VATS and robotic surgery."
Full details of the work appear in The Journal of Thoracic and Cardiovascular Surgery; for more information, please visit http://dx.doi.org/10.1016/j.jtcvs.2015.05.014.
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