Cathepsin B Triggered Hyperpolarization 129Xe MRI Probe for Ultra-Sensitive Lung Cancer Cells Detection

Abstract

Cathepsin B (Cat B) is a lysosomal cysteine protease that plays an essential role in cellular metabolism. Cat B is overexpressed in lung cancer cells. Fluorescence imaging techniques have been developed for measuring intracellular Cat B levels, which, however, suffers from limited penetration depth and interferences from autofluorescence background. To resolve these technical difficulties, we designed a novel Cat B biosensor detected by hyperpolarized xenon magnetic resonance imaging. It consists of a cryptophane cage as a 129Xe NMR reporter and an amide bond as a Cat B-specific cleavable group. When the biosensor interacts with Cat B, the cleavage of amide bond leads to changes in 129Xe chemical shift. Combing with hyperpolarization-chemical exchange saturation transfer (Hyper-CEST), our biosensor provides a novel method for responsive detection of Cat B.

Keywords

• nuclear magnetic resonance (nmr)
• contrast agents
• lung cancer
• hyperpolarization 129xe mri probe
• cathepsin b
• chemical exchange saturation transfer (cest)