Abstract 4102: Surgical imaging of pancreatic cancer using near infrared fluorescent hyaluronic acid nanomaterials
Authors: Bowen Qi, Ayrianne Crawford, Samuel Cohen, Michael Hollingsworth, Aaron M. Mohs
Journal: Cancer Research (2018)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) has an overall 5-year survival rate for all patients of approximately 7.1%. Surgery only increases the long-term survival rate of PDAC to 12.1%. Survival could potentially be increased with better detection of pancreatic cancer during surgical resection by improved margin detection, more effective debulking of disseminated disease, and earlier detection. In this work, we utilized nanoparticle formulations of the near infrared fluorophore indocyanine green (ICG) to provide optical detection of pancreatic tumors in an orthotopic, syngeneic mouse model of PDAC. Methods: ICG was physico-chemically entrapped nanoparticles derived from amphiphilic hyaluronic acid, termed NanoICG and compared to ICG alone. Cytotoxicity and immunotoxicity of the imaging agents were determined by in vitro methods, while blood biochemistry, cell counts, and toxicological pathology, were examined in vivo. The ability to detect PDAC was determined in PDAC cells originating from KPC mice that were implanted orthotopically into syngeneic C57 mice. Contrast enhancement was determined using a combination of image-guided surgery systems and whole animal imaging systems. Results: Neither Empty NP of NanoICG affected metabolic activity toward healthy pancreatic epithelial or pancreatic adenocarcinoma cells and NanoICG displayed did not have capacity to act as a chemoattractant. In vivo, NanoICG (normalized to maximum allowed ICG dose) did not alter blood biochemical markers including HGB, ALB, ALP, ALT, AMY, BUN, GLOB, and TP or cell counts including, WBC, RBC, PLT, or HCT. Histological examination showed no toxicity related to the administration of contrast agents in liver, lung, spleen, or kidneys. In the syngeneic, orthotopic PDAC model, NanoICG accumulated significantly within the pancreas and had a 2.1-fold stronger signal compared to ICG alone. Considering contrast within PDAC compared to uninvolved healthy pancreas, NanoICG was 2.34-fold stronger (P&amp;lt;0.05), while contrast between PDAC and healthy pancreas with ICG was minimally detectable. Using near infrared fluorescence microscopy, area strong signal from NanoICG localized to areas of PDAC. Conclusions: NanoICG exhibited improved efficacy at detecting pancreatic tumors in an orthotopic pancreatic cancer model with negligible NP-derived toxicity, which shows NanoICG as a promising agent in pancreatic tumor diagnosis and surgical resection. Further research is being performed to minimize clearance organ uptake.&amp;lt;!–EndFragment–&amp;gt; Citation Format: Bowen Qi, Ayrianne Crawford, Samuel Cohen, Michael Hollingsworth, Aaron M. Mohs. Surgical imaging of pancreatic cancer using near infrared fluorescent hyaluronic acid nanomaterials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4102.