Abstract 3729: Tumor-specific antibody labeling of pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model using a fluorescent humanized anti-CEA antibody

Abstract

Abstract Introduction: Delineation of tumor margins is critical in oncologic surgery, particularly in resection of pancreatic cancer. Surgeons are limited in visualization with bright light surgery. Fluorescence guided surgery (FGS) can help surgeons better visualize all potential cancer cells during the operation. In the present study, we show that the use of an anti-CEA antibody conjugated to an 800nm NIR fluorescent dye can selectively label pancreatic cancer in both pancreatic cancer cell lines and patient derived xenograft mouse models (PDOX). Materials/Methods: BxPC3-GFP cells or pancreatic cancer tissue specimens were grafted into flanks of nude mice. Both types of tumors were allowed to grow until 1 cm. Fragments tumors (2 mm3) were grafted onto the pancreatic tail of recipient mice to create PDOX models. After tumors reached 7-10mm in size, 75 ug of Anti-CEA-800 dye was injected into the tail-vein (LI-COR 800 CW IRDye®, Lincoln, NE). Mice were imaged via the Maestro CRI imaging system (Perkin Elmer, Waltham, MA) 24 hours after injection. Results: Images obtained after fluorescent antibody injection showed that anti-CEA-800 specifically labeled both the cell-line-derived tumors and patient-derived tumors with an adequate tumor to background contrast at 24 hours. The dye co-localized with GFP in tagged tumor cells lines. GFP fluorescence had poor penetration if covered by overlying tissue, which was not an issue with the anti-CEA-800 dye. The dye allowed clear identification of the tumor and tumor margin. In the BxPC-3 based tumor, the dye allowed identification of a small 1mm satellite lesion in the spleen that would otherwise have been missed. Conclusions: Fluorescent humanized anti-CEA-800 antibody specifically labeled orthotopically implanted pancreatic cancer xenografts from cell lines and patient derived tissue. Tumor-specific fluorescence imaging clearly identified the primary tumor and satellite lesion. The 800nm wavelength allowed deeper tissue penetration, particularly in areas of tumor covered by normal pancreatic parenchyma. Humanized anti-CEA antibodies conjugated to a radio-labeling agent and LI-COR 800 dye is already in Phase I/II trials. Humanized anti-CEA conjugated with the IR-800 dye is a promising agent for future clinical FGS applications. Citation Format: Thinzar Lwin, Takashi Murakami, Robert M. Hoffman, Paul J. Yazaki, Michael Bouvet. Tumor-specific antibody labeling of pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model using a fluorescent humanized anti-CEA antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3729. doi:10.1158/1538-7445.AM2017-3729