A Highly Sensitive PSMA-Targeted Ratiometric NIR Probe for Rapid Imaging of Prostate Cancer Acidity in Living Mice

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Oncology

Background:

• Acidic extracellular pH (pHe) is linked to tumor malignancy and resistance.
• Real-time, noninvasive imaging of tumor pHe dynamics is challenging.

Purpose of the Study:

• Develop a novel ratiometric near-infrared fluorescent probe for prostate cancer acidity imaging.
• Target prostate-specific membrane antigen (PSMA) for enhanced specificity and imaging.

Main Methods:

• Designed a small-molecule probe (PSMA-ratio-pH) with a pKa of 6.4.
• Evaluated probe characteristics including sensitivity, reversibility, photostability, and selectivity.
• Validated probe performance in cellular experiments and in vivo prostate cancer mouse models.

Main Results:

• The PSMA-ratio-pH probe demonstrated high sensitivity, good reversibility, and concentration-independent response.
• Specific anchoring to PSMA on cancer cells and reliable pHe sensing were confirmed.
• In vivo imaging in mice showed rapid tumor targeting and ratiometric acidity visualization within 15 minutes.

Conclusions:

• The PSMA-ratio-pH probe enables real-time, precise visualization of tumor microenvironment acidity.
• This molecular tool offers potential for cancer diagnosis and treatment evaluation.
• The probe facilitates monitoring of dynamic pH changes in tumor acidosis.