Intraoperative Molecular Imaging Utilizing a Folate Receptor-Targeted Near-Infrared Probe Can Identify Macroscopic Gastric Adenocarcinomas.

Abstract

Current methods of assessing disease burden in gastric adenocarcinoma are imperfect. Improved visualization during surgery with intraoperative molecular imaging (IMI) could improve gastric adenocarcinoma staging and guide surgical decision-making. The goal of this study was to evaluate if IMI with a folate receptor-targeted near-infrared fluorescent agent, OTL38, could identify gastric adenocarcinomas during surgery. Five patients were enrolled in an IMI clinical trial. Patients received a folate receptor-targeted near-infrared dye (OTL38) 1.5-6h prior to surgery. During staging laparoscopy and gastric resection, IMI was utilized to identify the primary tumor and any fluorescent lymph nodes. Resected tumors were analyzed for folate receptor alpha (FRα) and CD68 expression using immunohistochemistry. Microscopic OTL38 accumulation was examined with immunofluorescence. Four out of five patients underwent total or subtotal gastrectomy; one had a staging laparoscopy only. All four patients who underwent gastric resection had invasive gastric adenocarcinoma; three had fluorescent tumors, mean tumor to background ratio (TBR) 4.1 ± 2.9. The one patient with a non-fluorescent tumor had a T1a tumor with two 0.4cm tumor foci within a larger polyp. In each case with a fluorescent tumor, the fluorescence was evident from the exterior of the stomach. Two of the fluorescent tumors had modest FRα expression and no CD68 expression. One fluorescent tumor had high CD68 expression and no FRα expression. Intraoperative molecular imaging of gastric adenocarcinoma with OTL38 is feasible. Further studies should evaluate the clinical utility of this technique.