An open label trial of folate receptor-targeted intraoperative molecular imaging to localize pulmonary squamous cell carcinomas

• Type of Material: Article
• Authors: Jarrod Predina, University of Pennsylvania; Andrew Newton, University of Pennsylvania; Leilei Xia, University of Pennsylvania; Christopher Corbett, University of Pennsylvania; Courtney Connolly, University of Pennsylvania; Michael Shin, University of Pennsylvania; Lydia Frezel Sulyok, University of Pennsylvania; Leslie Litzky, University of Pennsylvania; Charuhas Deshpande, University of Pennsylvania; Shuming Nie, Emory University; Shuming Kularatne, Purdue University College of Science; Phillip Low, Purdue University College of Science; Sunil Singhal, University of Pennsylvania
• Language: English
• Date: 2018-01-01
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © Predina et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.24399
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 9
• Issue: 17
• Start Page: 13517
• End Page: 13529
• Grant/Funding Information: SS was supported by the NIH (R01 CA193556).; JDP as supported by a grant from the American Philosophical Society, the NIH (1F32CA210409), and the Association for Academic Surgery Research Grant.
• Keywords: folate receptor; surgery; squamous cell carcinoma; molecular imaging
• Research Categories: Engineering, Biomedical; Health Sciences, Oncology

Abstract

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 receptoralpha 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.