TY - JOUR
T1 - Localization of Pulmonary Ground-Glass Opacities with Folate Receptor–Targeted Intraoperative Molecular Imaging
AU - Predina, Jarrod D.
AU - Newton, Andrew
AU - Corbett, Christopher
AU - Xia, Leilei
AU - Sulyok, Lydia Frenzel
AU - Shin, Michael
AU - Deshpande, Charuhas
AU - Litzky, Leslie
AU - Barbosa, Eduardo
AU - Low, Philip S.
AU - Kucharczuk, John C.
AU - Singhal, Sunil
N1 - Funding Information:
Dr. Predina was supported by the American Philosophical Society, the National Institutes of Health (grant F32CA210409 ), and an Association for Academic Surgery research grant. Dr. Singhal was supported by the National Institutes of Health (grant R01 CA193556 ). Dr. Predina and Dr. Singhal participated in study design, data collection, data analysis, manuscript preparation, and manuscript review. Dr. Newton, Mr. Corbett, Ms. Sulyok, Mr. Shin, and Dr. Kucharczuk participated in data collection, data analysis, and manuscript review. Dr. Deshpande, Dr. Barbosa, and Dr. Low assisted in data collection, data analysis, manuscript preparation, and manuscript review.
Publisher Copyright:
© 2018 International Association for the Study of Lung Cancer
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
KW - Fluorescence-guided surgery
KW - Folate receptor
KW - Ground-glass opacity
KW - Lung cancer
KW - Molecular imaging
KW - Surgery
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U2 - 10.1016/j.jtho.2018.03.023
DO - 10.1016/j.jtho.2018.03.023
M3 - Article
C2 - 29626619
AN - SCOPUS:85048742010
VL - 13
SP - 1028
EP - 1036
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 7
ER -