Bridging the Resolution Gap in Recurrent Prostate Cancer Imaging: Quantum Dots as PSMA-Targeted Optical Probes.

Recurrent prostate cancer (RPC) remains a major clinical challenge driven by residual and disseminated tumor cells exhibiting pronounced molecular and spatial heterogeneity. Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography enables sensitive whole-body detection of recurrent lesions; however, its millimeter-scale spatial resolution and limited multiplexing capacity constrain the characterization of cellular heterogeneity and micrometastatic disease. Quantum dots (QDs) are nanoscale optical probes with high brightness, exceptional photostability, and narrow, size-tunable emission spectra, enabling multiplexed molecular imaging at subcellular resolution. When functionalized with PSMA-targeting ligands, QDs facilitate the sensitive and spatially resolved visualization of PSMA expression, supporting the detection of heterogeneous and low-abundance tumor cell populations. Among QD platforms, cadmium-based systems offer superior optical performance for multiplexed imaging, whereas cadmium-free and carbon-based QDs provide improved biocompatibility and greater translational potential. Nevertheless, challenges related to toxicity, biodistribution, and clearance remain significant barriers to clinical application. This Review highlights QDs as complementary optical probes that may bridge the resolution gap between whole-body imaging and cellular-scale analysis, with particular relevance for preclinical research, ex vivo tissue interrogation, and intraoperative imaging. Collectively, QD-based strategies provide a conceptual framework for enhancing molecularly specific, high-resolution visualization in RPC imaging workflows.