Real-time In Vivo Molecular Detection of Primary Tumors and Metastases with Ratiometric Activatable Cell-Penetrating Peptides
Year: 2012
Type: article
Abstract: Management of metastatic disease is integral to cancer treatment. Evaluation of metastases often requires surgical removal of all anatomically susceptible lymph nodes for ex vivo pathologic examination. We report a family of novel ratiometric activatable cell-penetrating peptides, which contain Cy5 as far red fluorescent donor and Cy7 as near-infrared fluorescent acceptor. Cy5 is quenched in favor of Cy7 re-emission until the intervening linker is cut by tumor-associated matrix metalloproteinases-2 and 9 (MMP2,9) or elastases. Such cleavage increases the Cy5:Cy7 emission ratio 40-fold and triggers tissue retention of the Cy5-containing fragment. This ratiometric increase provides an accelerated and quantifiable metric to identify primary tumors and metastases to liver and lymph nodes with increased sensitivity and specificity. This technique represents a significant advance over existing nonratiometric protease sensors and sentinel lymph node detection methods, which give no information about cancer invasion.
Source: Cancer Research
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Awards: Testing Surgery Guided by Molecular Fluorescence Imaging, Injectable reporters to image tumors and guide resection, UCSD Cancer Nanotechnology Training Center, Testing Fluorescently Labeled Probes for Nerve Imaging during Surgery, In Vivo Cellular and Molecular Imaging Centers (ICMICs), Medical Scientist Training Program
OpenAlex ID: W2002767447