PSMA-Targeted Intracellular Self-Assembled Probe for Enhanced PET Imaging.

Positron-emission tomography (PET) offers high sensitivity for cancer diagnosis. However, small-molecule-based probes often exhibit insufficient accumulation in tumor sites, while nanoparticle-based agents typically have limited delivery efficiency. To address this challenge, this study proposes a novel PET imaging probe, ⁶⁸Ga-CBT-PSMA, designed for prostate cancer. This probe integrates an intracellular self-assembly strategy to enhance PET imaging signals and significantly improve the signal-to-noise ratio. The glutamate-urea-based prostate-specific membrane antigen (PSMA)-targeting motif enables specific recognition of prostate cancer cells and enhances cellular uptake; then the self-assembly process induced by glutathione reduction effectively accumulates the probe within tumor cells, thereby amplifying PET imaging signals. This approach not only enhances signal intensity and resolution but also facilitates precise cancer localization and diagnosis, offering new avenues for advancing cancer diagnostic techniques.