Molecular imaging of Cathepsin E-positive tumors in mice using a novel protease-activatable fluorescent probe.

ABSTRACT: The purpose of this study is to demonstrate the ability of imaging Cathepsin E (Cath E) positive tumors in living animals through selective targeting of Cath E proteolytic activity using a sensitive molecular imaging agent.A peptide-based Cath E imaging probe and a control probe were synthesized for this study. Human Cath E-positive cancer cells (MPanc96-E) were implanted subcutaneously in nude mice. Tumor-bearing mice were examined in vivo with near-infrared fluorescence (NIRF) imaging at various time points after intravenous injection of the Cath E sensing imaging probe. Excised organs and tissues of interest were further imaged ex vivo.Upon specific Cath E proteolytic activation, the NIRF signal of the imaging probe a was converted from an optically quenched initial state to a highly fluorescent active state. Imaging probe a was able to highlight the Cath E-positive tumors as early as 24 h post injection. Fluorescent signal in tumor was 3-fold higher than background. The confined specificity of imaging probe a to tumor associated Cath E was verified by using control imaging probe b. Both in vivo and ex vivo imaging results confirmed the superior selectivity and sensitivity of imaging probe a in Cath E imaging.The small animal studies demonstrated the capability of probe a for imaging Cath E-positive tumors. The developed optical probe could be applied in early diagnostic imaging and guiding subsequent surgical procedure.

SUBMITTER: Abd-Elgaliel WR 

PROVIDER: S-EPMC4207267 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature