“Crossbreeding” NIR‐II flavchromene for PSMA‐positive prostate cancer detection and image‐guided surgery

Prostate‐specific membrane antigen (PSMA) is known to be overexpressed in prostate cancer (PCa). The development of precise and rapid imaging technologies to monitor PSMA is crucial for early diagnosis and therapy. Fluorescence imaging in the second near‐infrared window (NIR‐II) has emerged as a powerful tool for real‐time tracking and in vivo visualization, offering high sensitivity and resolution. However, there is a lack of stable, bright and easy‐to‐implement NIR‐II fluorescent probes for PSMA targeting. Herein, we presented a PSMA‐targeting NIR‐II fluorescent probe FC‐PSMA based on π‐conjugated crossbreeding dyed strategy that affords high stability, large extinction coefficient, and good brightness. As demonstrated, FC‐PSMA displayed a high fluorescence quantum yield in fetal bovine serum (FBS). Following intravenous injection of FC‐PSMA, the tumor‐to‐normal ratio of fluorescence intensity steadily increased over time, reaching a peak at 48 h (tumor‐to‐leg ratio = 12.16 ± 0.90). This advancement enables precise identification of PC through NIR‐II fluorescence imaging, facilitating high‐performance guidance for prostate cancer resection surgery.