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

Created on 12 Jul 2026

Authors

Xuekang Cai, Jingming Zhang, Wenhui Huang, Xiaojiang Duan, Lei Kang

Published in

Chemistry (Weinheim an der Bergstrasse, Germany). Pages e71411. Jul 12, 2026. Epub Jul 12, 2026.

Abstract

Acidic extracellular pH (pHe), a hallmark of the solid tumor microenvironment, is closely associated with increased tumor malignancy and therapy resistance. However, the real-time, noninvasive visualization of dynamic pHe changes in vivo remains a formidable technical challenge. In this study, we developed a novel small-molecule ratiometric near-infrared fluorescent probe PSMA-ratio-pH targeting the prostate-specific membrane antigen (PSMA), designed to enable rapid and precise imaging of prostate cancer acidity in living mice. This probe exhibits a pKa of 6.4, a value well-suitable for tumor acidity detection, along with dual near-infrared emission, high sensitivity (1250-fold activation), good reversibility, concentration-independent response, robust photostability, and high selectivity. Cellular experiments confirmed its specific anchoring to PSMA on the cell membrane and reliable sensing of pHe. In mouse models of prostate cancer, the probe achieved rapid tumor targeting and ratiometric acidity imaging within 15 min post intravenous injection owing to favorable pharmacokinetics and high PSMA affinity, and was capable of monitoring dynamic pH changes in tumor acidosis. This research provides a powerful molecular tool for the real-time and precise visualization of tumor microenvironment acidity, holding broad application prospects in cancer diagnosis and treatment evaluation.

PMID:
42437392
Bibliographic data and abstract were imported from PubMed on 12 Jul 2026.

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