Improved surgical resection of metastatic pancreatic cancer using uPAR targeted <i>in vivo</i> fluorescent guidance: comparison with traditional white light surgery

Abstract

// Karina Juhl 1 , 2 , Anders Christensen 1 , 2 , 3 , Niclas Rubek 3 , Kirstine Kim Schmidt Karnov 1 , 2 , 3 , * , Christian von Buchwald 3 and Andreas Kjaer 1 , 2 1 Department of Clinical Physiology, Nuclear Medicine &amp; PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2 Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark 3 Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark * Kirstine Kim Schmidt Karnov sadly passed away before publishing of this article. We will miss her and our thoughts are with her family Correspondence to: Andreas Kjaer, email: [email protected] Keywords: optical imaging; near-infrared imaging (NIR); NIR-I; urokinase plasminogen activator receptor (uPAR); cancer Received: April 26, 2019&emsp;&emsp;&emsp;&emsp; Accepted: August 22, 2019&emsp;&emsp;&emsp;&emsp; Published: October 29, 2019 ABSTRACT Pancreatic cancer remains one of the deadliest cancers. The five-year survival rates have been reported as 3%. Radical surgical tumor resection is critical for improved outcome and the low survival rate for pancreatic cancer is due to lack of other effective treatments and here optical guided surgery could be a solution for better surgical outcome. In the present study, we targeted the urokinase plasminogen activator receptor (uPAR) with a peptide conjugated with the fluophore ICG (ICG-Glu-Glu-AE105) for optical imaging. In the first part of the study we aimed to validate ICG-Glu-Glu-AE105 for resection of the primary tumor and metastases in an orthotopic human xenograft pancreatic cancer model. In the second part of the study we aimed to investigate if fluorescent-guided imaging could locate additional metastases following conventional removal of metastasis under normal white light surgery. Our study showed that ICG-Glu-Glu-AE105 was an excellent probe for intraoperative optical imaging with a mean tumor-to-background ratio (TBR) for the primary tumor of 3.5 and a TBR for the metastases of 3.4. Further, a benefit using intraoperative fluorescent guidance yielded identification of an additional 14% metastases compared to using normal white light surgery. In 4 of 8 mice there were identified additional metastases with uPAR optical imaging compared to white light. In conclusion, the uPAR-targeted optical probe ICG-Glu-Glu-AE105 enables intraoperative optical cancer imaging, including robotic surgery, and may be a benefit during intended radical resection of disseminated pancreas cancer by finding more metastasis than with traditional white light surgery.