Jarrod D Predina1, Andrew Newton1, Christopher Corbett1, Leilei Xia2, Lydia Frenzel Sulyok1, Michael Shin1, Charuhas Deshpande3, Leslie Litzky3, Eduardo Barbosa4, Philip S Low5, John C Kucharczuk1, Sunil Singhal6. 1. Center for Precision Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 2. Center for Precision Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 4. Center for Precision Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. 5. Department of Chemistry, Purdue University, West Lafayette, Indiana; Purdue Institute for Drug Discovery, Purdue University, West Lafayette, Indiana. 6. Center for Precision Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: Sunil.singhal@uphs.upenn.edu.
Abstract
PURPOSE: Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins. METHODS: In a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging. RESULTS: We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited. CONCLUSIONS: This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial.
PURPOSE: Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins. METHODS: In a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging. RESULTS: We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited. CONCLUSIONS: This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial.
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