Surgery is an efficient way to treat localized prostate cancer (PCa), however, it is challenging to demarcate rapidly and accurately the tumor boundary intraoperatively, as existing tumor detection methods are seldom performed in real-time. To overcome those limitations, we develop a fluorescent molecular rotor that specifically targets the prostate-specific membrane antigen (PSMA), an established marker for PCa. The probes have picomolar affinity (IC50 = 63-118 pM) for PSMA and generate virtually instantaneous onset of robust fluorescent signal proportional to the concentration of the PSMA-probe complex. In vitro and ex vivo experiments using PCa cell lines and clinical samples, respectively, indicate the utility of the probe for biomedical applications, including real-time monitoring of endocytosis and tumor staging. Experiments performed in a PCa xenograft model reveal suitability of the probe for imaging applications in vivo.

Beijing Key Laboratory of Urogenital Diseases Molecular Diagnosis and Treatment Center 10034 Beijing China

Department of General Surgery Peking University 1st Hospital 100034 Beijing China

Department of Nuclear Medicine Peking University 1st Hospital 100034 Beijing China

Department of Urology Peking University 1st Hospital 100034 Beijing China

Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Prumyslova 595 25250 Vestec Czech Republic

Institute of Medical Technology Peking University Health Science Center 100191 Beijing China

Key Laboratory of Carcinogenesis and Translational Research Department of Nuclear Medicine Peking University Cancer Hospital and Institute 100142 Beijing China

National Urological Cancer Center 100034 Beijing China

Russell H Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore MD 21205 USA

State Key Laboratory of Natural and Biomimetic Drugs Peking University 100191 Beijing China

The Institute of Urology Peking University 100034 Beijing China

Translational Cancer Research Center Peking University 1st Hospital 100034 Beijing China

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