Abstract

Abstract The aim of this study was to improve detection of primary and metastatic lesions of human pancreatic cancer in mouse models with fluorescence laparoscopy by enhancing the fluorescence signal of tumor with different combinations of fluorophores without compromising background illumination. Human pancreatic cancer models were established with combinations of FG-RFP, MiaPaca2-GFP, BxPC-3-RFP, or BxPC-3 cancer cells implanted in 6-week-old female athymic mice. Two weeks post-implantation, diagnostic laparoscopy was performed with a Stryker L9000 LED light source 24 hours after tail vein injection of CEA antibodies conjugated with Alexa 488- and/or Alexa 555. Cancer lesions were detected and localized under the fluorescence light mode. Intravital images were obtained with the Maestro CRI Small Animal Imaging System, serving as a positive control. Tumors were collected for histologic review. Fluorescence laparoscopy with a 495-nm emission filter and an LED light source enabled real-time visualization of differently fluorescence-labeled tumors in the peritoneal cavity simultaneously. The combination of BxPC-3 RFP labeled with anti-CEA-Alexa 488 afforded the brightest signal of all established mouse models. We were able to reproduce this enhanced fluorescence signaling by doubly labeling non-color BxPC-3 tumor with anti-CEA-Alexa 488 and anti-CEA-Alexa 555. The doubly labeled tumor provided a greater signal intensity profile compared to tumors labeled with either anti-CEA-Alexa 488 or -Alexa 555 alone. This enhanced fluorescence signal permitted improved detection of sub-millimeter lesions without compromising background illumination. The ability to visualize tumor deposits expressing fluorescent proteins of different wavelengths simultaneously with an LED light source enabled us to establish the optimal combination of fluorophores that enhanced the signal intensity of fluorescence. With this optimal fluorophore combination, we improved the detection of sub-millimeter tumor lesions without impairing the visualization of surrounding structures necessary for surgical navigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 369. doi:1538-7445.AM2012-369

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