Development of a Dual-Factor Activatable Covalent Targeted Photoacoustic Imaging Probe for Tumor Imaging.

Area of Science:

• Biomedical imaging
• Molecular imaging
• Biochemistry

Background:

• Photoacoustic imaging (PAI) offers deep tissue penetration and high specificity.
• Existing PAI faces challenges with background noise from endogenous chromophores.
• NCEH1, a serine hydrolase, is upregulated in aggressive cancers, presenting a diagnostic target.

Purpose of the Study:

• To develop a novel covalent activity-based PAI probe, NOx-JS013, targeting NCEH1.
• To assess the probe's selectivity and efficacy in detecting active NCEH1.
• To evaluate NOx-JS013 as a hypoxia-responsive probe and for in vivo tumor imaging.

Main Methods:

• Development of a covalent activity-based PAI probe (NOx-JS013).
• In vitro testing for selective labeling of active NCEH1 in live cells.
• In vivo imaging of prostate cancer xenografts in mouse models (PC3 and LNCaP).

Main Results:

• NOx-JS013 selectively labels active NCEH1 in live cells with high specificity.
• The probe demonstrates hypoxia-responsive imaging capabilities in live cells.
• NOx-JS013 successfully visualizes aggressive PC3 prostate tumors in vivo, with minimal signal in non-aggressive LNCaP tumors.

Conclusions:

• NOx-JS013 is a selective, hypoxia-responsive PAI probe for active NCEH1.
• The probe shows potential for precise in vivo imaging of aggressive cancers.
• NOx-JS013 could be developed into advanced PAI reagents for detecting cancer metastasis.