Preclinical evaluation of near‐infrared (NIR) fluorescently labeled cetuximab as a potential tool for fluorescence‐guided surgery. Issue 10 (16th August 2016)

• Record Type: Journal Article
• Authors: Saccomano, Mara; Dullin, Christian; Alves, Frauke; Napp, Joanna
• Is Part Of: International journal of cancer. Volume 139:Issue 10(2016:Nov. 15)
• Page Start: 2277
• Page End: 2289
• Publication Date: 2016-08-16
• Subjects: Cetuximab -- near‐infrared fluorescence -- fluorescence‐guided surgery (FGS) -- IRDye 800CW -- clinical translation -- pancreatic ductal adenocarcinoma (PDAC) -- orthotopic pancreatic tumor mouse models; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30277
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : The high rate of recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) could be reduced by supporting the surgeons in discriminating healthy from diseased tissues with intraoperative fluorescence‐guidance. Here, we studied the suitability of Cetuximab, a therapeutic monoclonal antibody targeting the human epidermal growth factor receptor (EGFR), near‐infrared (NIR) fluorescently labeled as a new tool for fluorescence‐guided surgery. Distribution and binding of systemically injected Cetuximab Alexa Fluor 647 conjugate (Cetux‐Alexa‐647) and the co‐injected control human IgG Alexa Fluor 750 conjugate (hIgG‐Alexa‐750) was studied over 48 h by NIR fluorescence imaging in mice bearing human orthotopic AsPC‐1 and MIA PaCa‐2 PDAC tumors. Cetux‐Alexa‐647, but not the control hIgG‐Alexa‐750 fluorescence, was specifically detected in vivo in both primary pancreatic tumors with maximum fluorescence intensities at 24 h, and in metastases of AsPC‐1 tumors as small as 1 mm. Lifetime analysis and NIR fluorescence microscopy of tumor sections confirmed the binding specificity of Cetux‐Alexa‐647 to PDAC cells. Comparable results were obtained with Cetuximab conjugated to Alexa Fluor 750 dye (Cetux‐Alexa‐750). Fluorescence‐guided dissection, performed 24 h after injection of Cetuximab conjugated to IRDye 800CW (Cetux‐800CW), enabled a real‐time delineation of AsPC‐1 tumor margins, and small metastases. Odyssey scans revealed that only the vital part of the tumor, but not the necrotic part was stained with Cetux‐800CW. NIR fluorescently labeled Cetuximab may be a promising tool that can be applied for fluorescence‐guided surgery to visualize tumor margins and metastatic sites in order to allow a precise surgical resection. Abstract : What's new? The combination of cancer‐specific fluorescent labels and fluorescence‐guided surgery (FGS) is a promising approach to improve the visualization of tumor margins and metastatic sites during surgery to remove cancer. This study shows that precise surgical resection is facilitated significantly by the use of near‐infrared fluorescently labeled Cetuximab (Cetux‐800CW), a therapeutic antibody targeting the epidermal growth factor receptor. In mice bearing pancreatic ductal adenocarcinomas, Cetux‐800CW enabled clear delineation of tumor margins and detection of invasive nodules in the stomach, duodenum, and other organs. Cetux‐800CW, through improving the precision of tumor margin assessment, could help reduce the likelihood of recurrence following surgery.