Abstract
The recurrence of certain cancers remains quite high due to either incomplete surgical removal of the primary tumor or the presence of small metastases that are invisible to the surgeon. Near infrared (NIR) fluorescence imaging might improve surgical outcomes by providing sensitive, specific, and real-time visualization of normal and diseased tissues if agents can be found that discriminate between normal and diseased tissue and define tumor margins. We have developed a new approach for revealing tumor borders by using NIR fluorescently labeled pH Low Insertion Peptide (pHLIP) and have created a computational program for the quantitative assessment of tumor boundaries. The approach is tested in vivo by co-localization of GFP-tumors and NIR emission from the fluorescently labeled pHLIP, and it is found that boundaries are accurately reported and that sub-millimeter masses can be detected.
Highlights
In contemporary medicine, image-guided surgery has been introduced to maximize tumor excision and minimize collateral damage
We have demonstrated that pH Low Insertion Peptide, targets acidic tissues in vivo, and can be used to localize molecules at cell surfaces or to translocate otherwise cell-impermeable cargo molecules into cells [14,15,16,17]. pHLIP, when conjugated with various fluorescent and positron emission tomography imaging agents, can accumulate in tumors of various types established in mice [14,15,16]
Our goals are to test the ability of fluorescent pHLIP to reveal tumor borders and to develop a computer program for the quantitative assessment of the co-localization of green fluorescent protein (GFP)-tumors and the pHLIP
Summary
Image-guided surgery has been introduced to maximize tumor excision and minimize collateral damage. Optical techniques might be useful if the fluorescence signal is collected from a surface, as in a surgical setting where diseased tissue is exposed to view, but only if an optical imaging agent can preferentially and accurately target cancer cells. Tumor acidity, which is a feature of most solid tumors, might be an attractive cancer biomarker if means can be found to target cells in low pH environments [13]. We have demonstrated that pH Low Insertion Peptide (pHLIP), targets acidic tissues in vivo, and can be used to localize molecules at cell surfaces or to translocate otherwise cell-impermeable cargo molecules into cells [14,15,16,17]. We demonstrate that fluorescent pHLIP targets cancer cells to effectively mark their boundaries, and present a specially designed computational program that reveals tumor borders with high accuracy
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