Introduction: Each year, nearly 100,000 patients proceed to the operating room for pulmonary resection, though identification of pulmonary nodules can frequently be challenging. We hypothesize that targeted intraoperative molecular imagining can improve identification of pulmonary nodules at the time of surgery. To test the safety of our novel targeted optical contrast agent, we have performed a Phase I trial.
Methods: OTL38 is a near-infrared imaging agent that targets FRα, a receptor upregulated by 10,000-fold in 85-90% of patients with pulmonary adenocarcinoma. Twenty patients with a biopsy-proven lung adenocarcinoma were enrolled in a Phase I clinical trial. Prior to surgery, patients were systemically administered OTL38 (0.0025mg/kg) by intravenous infusion. During surgery, tumors were imaged in situ and ex vivo. Tumor fluorescence was quantified using tumor-to-background ratio (TBR).
Results: In human patients receiving OTL38 prior to resection, we observed only minor Grade 1 toxcities: itching and a rash. We identified 18 nodules (90%) in 20 patients, and the mean tumor size was 2.5 cm (range 0.5-10.5cm). 22% of the fluorescent nodules measured less than 1cm. Mean TBR of fluorescent tumors was 3.2 (range 1.7-4.6). Tumor size did not correlate with TBR (p>0.05). In 2 patients, intraoperative imaging identified synchronous subcentimeter (5mm, 9mm) nodules which were not detected by pre-operative CAT or PET scanning.
Conclusion: Our Phase I clinical trial showed targeted molecular imaging with OTL38 is safe and has only minor Grade I toxicities. In addition, this study showed that the optical contrast agent is capable of detecting subcentimeter pulmonary nodules in humans. Our group is currently conducting a multicenter, Phase II study to better understand the implications of intraoperative molecular imaging using OTL38.