Abstract
We report here that polyethylene glycol (PEG) linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases.
Highlights
The use of fluorescence imaging has become widespread in mouse models of cancer and has begun to make an impact in the clinical care of patients [1,2]
We imaged mice bearing HT-29 colon cancer liver metastases using anti-chimeric mouse-human anticarcinoembryonic antigen (CEA) antibody labeled with 650-polyethylene glycol (PEG) (Figure 4a) or 750-PEG (Figure 4b)
We demonstrated that PEG conjugation of Near Infrared (NIR) dyes conjugated to a chimeric anti-CEA antibody enhances imaging of liver metastases in nude-mouse models
Summary
The use of fluorescence imaging has become widespread in mouse models of cancer and has begun to make an impact in the clinical care of patients [1,2]. Fluorescently-tagged tissues of interest allow for easy detection and demarcation from other structures in both living and fixed tissues. In living tissue this allows for differential imaging of cells or molecules without disrupting other biological processes and allows for real-time imaging [1]. In an effort to bring FGS to the clinic, we have developed FGS in orthotopic mouse models of pancreatic and colon cancer by labeling the tumor with tumorspecific monoclonal mouse antibodies conjugated to Alexa Fluor 488, a green fluorophore [12,13] as well as labeling with a tumorspecific adenovirus [11]. Minimally invasive fluorescence laparoscopy was used to successfully image orthotopic pancreatic tumors in mice labeled with fluorophore conjugated monoclonal mouse antibodies to CEA [14,15]
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