Abstract

We report here the development of fluorescence-guided surgery of liver metastasis. HT29 human colon cancer cells expressing green fluorescent protein (GFP) were initially injected in the spleen of nude mice. Three weeks later, established liver metastases were harvested and implanted on the left lobe of the liver in other nude mice in order to make an orthotopic liver metastasis model. Fourteen mice with a single liver metastasis were randomized into bright-light surgery (BLS) or fluorescence-guided surgery (FGS) groups. Seven mice were treated with BLS, seven were treated with FGS. Three weeks after implantation, the left lobe of the liver with a single metastasis was exposed through a median abdominal incision. BLS was performed under white light. FGS was performed using a hand-held portable fluorescence imaging system (Dino-Lite). Post-surgical residual tumor fluorescence was visualized with the OV100 Small Animal Imaging System. Residual tumor fluorescence after BLS was clearly visualized at high magnification with the OV100. In contrast, residual tumor fluorescence after FGS was not detected even at high magnification with the OV100. These results demonstrate the feasibility of FGS for liver metastasis.

Highlights

  • IntroductionThe ability of the surgeon to accurately visualize tumor margins is essential at the time of surgery and is of particular importance for resection of metastatic disease, especially in the liver [1]

  • The ability of the surgeon to accurately visualize tumor margins is essential at the time of surgery and is of particular importance for resection of metastatic disease, especially in the liver [1].A variety of labeling compounds have been used for fluorescence-guided surgery in the clinic

  • All animal studies were conducted with an AntiCancer Institutional Animal Care and Use Committee (IACUC)-protocol approved for this study and in accordance with the principals and procedures outlined in the National Institute of Health Guide for the Care and Use of Animals under Assurance Number A3873-1

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Summary

Introduction

The ability of the surgeon to accurately visualize tumor margins is essential at the time of surgery and is of particular importance for resection of metastatic disease, especially in the liver [1]. A variety of labeling compounds have been used for fluorescence-guided surgery in the clinic. Sentinel lymph nodes in breast cancer patients were labeled by a near-infrared (NIR) fluorescing dye indocyanine [2]. The metabolite 5-aminolevulinic acid, a precursor of hemoglobin, labels porphyrins in malignant glioma for FGS [3], which significantly improved outcome. Folate was coupled to fluorescein isothiocyanate (FITC) for targeting folate receptor–α (FRα) in ovarian cancers. Under fluorescence-guided surgery, tumor deposits less than 1 mm in size could be visualized and resected [4]

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