Measuring Tumor Aggressiveness and Targeting Metastatic Lesions with Fluorescent pHLIP

Authors

Yana K. Reshetnyak, University of Rhode IslandFollow
Lan Yao, University of Rhode Island
Sida Zheng, University of Rhode Island
Sergey Kuznetsov, University of Rhode Island
Donald M. Engelman
Oleg A. Andreev, University of Rhode IslandFollow

Document Type

Article

Date of Original Version

2011

Department

Physics

Abstract

Purpose: Malignant cancer foci develop acidic extracellular environments. Mild acidic conditions trigger insertion and folding of the pH (low) insertion peptide (pHLIP^TM) across a cellular membrane, enabling targeting of such lesions.

Procedures: We employed optical imaging to follow targeting by fluorescent pHLIP given i.v. in mice. For visualization, Cy5.5 and Alexa750 were covalently attached to the N terminus of pHLIP, which stays outside of a cell membrane after transmembrane insertion.

Results: We demonstrate that pHLIP targets: (a) tumors of different origins established by subcutaneous injection of cancer cells, (b) spontaneous prostate tumors in TRAMP mice and (c) metastatic lesions in lung pHLIP accumulation in tumors correlates with tumor aggressiveness. Within a tumor, it stains extracellular spaces and cellular membranes.

Conclusions: Tissue acidity can be detected by pHLIP peptide insertion and used to diagnose primary tumors, metastatic lesions, and lipid bodies in necrotic tissues. The ability of pHLIP to differentially bind metastatic and non-metastatic tumors may provide a new approach for evaluating cancer prognosis.

Citation/Publisher Attribution

Reshetnyak, Y.K., Yao, L., Zheng, S. et al. Mol Imaging Biol (2011) 13: 1146. https://doi.org/10.1007/s11307-010-0457-z

Available at: https://doi.org/10.1007/s11307-010-0457-z