An open label trial of folate receptor-targeted intraoperative molecular imaging to localize pulmonary squamous cell carcinomas
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Jarrod D. Predina1,2, Andrew D. Newton1,3, Leilei Xia1,4, Christopher Corbett1,3, Courtney Connolly1,2, Michael Shin1,2, Lydia Frezel Sulyok1,2, Leslie Litzky5, Charuhas Deshpande5, Shuming Nie6, Sumith A. Kularatne7, Philip S. Low7 and Sunil Singhal1,2
1Center for Precision Surgery, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA
2Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA
3Department of Surgery, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA
4Division of Urology, Department of Surgery, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA
5Pathology and Laboratory Medicine at The Hospital of The University of Pennsylvania, Philadelphia, PA, USA
6Department Biomedical Engineering and Winship Cancer Institute, Emory University, Atlanta, GA, USA
7Department of Chemistry, and Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA
Sunil Singhal, email: [email protected]
Keywords: squamous cell carcinoma; surgery; molecular imaging; folate receptor
Received: November 21, 2017 Accepted: January 09, 2018 Published: February 05, 2018
Background: Clinical applicability of folate receptor-targeted intraoperative molecular imaging (FR-IMI) has been established for surgically resectable pulmonary adenocarcinoma. A role for FR-IMI in other lung cancer histologies has not been studied. In this study, we evaluate feasibility of FR-IMI in patients undergoing pulmonary resection for squamous cell carcinomas (SCCs).
Methods: In a human clinical trial (NCT02602119), twelve subjects with pulmonary SCCs underwent FR-IMI with a near-infrared contrast agent that targets the folate receptor-α (FRα), OTL38. Near-infrared signal from tumors and benign lung was quantified to calculate tumor-to-background ratios (TBR). Folate receptor-alpha expression was characterized, and histopathologic correlative analyses were performed to evaluate patterns of OTL38 accumulation. An exploratory analysis was performed to determine patient and histopathologic variables that predict tumor fluorescence.
Results: 9 of 13 SCCs (in 9 of 12 of subjects) displayed intraoperative fluorescence upon NIR evaluation (median TBR, 3.9). OTL38 accumulated within SCCs in a FRα-dependent manner. FR-IMI was reliable in localizing nodules as small as 1.1 cm, and prevented conversion to thoracotomy for nodule localization in three subjects. Upon evaluation of patient and histopathologic variables, in situ fluorescence was associated with distance from the pleural surface, and was independent of alternative variables including tumor size and metabolic activity.
Conclusions: This work demonstrates that FR-IMI is potentially feasible in 70% of SCC patients, and that molecular imaging can improve localization during minimally invasive pulmonary resection. These findings complement previous data demonstrating that ~98% of pulmonary adenocarcinomas are localized during FR-IMI and suggest broad applicability for NSCLC patients undergoing resection.
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