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Visualizing Tumors in Real Time: A Highly Sensitive PSMA Probe for NIR-II Imaging and Intraoperative Tumor Resection
Longfei Zhang1, Xiaojing Shi2, Yuying Li1
1Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
Abstract:
Owing to the complex anatomical structure, precise resection of a tumor while maintaining adjacent tissue is a challenge in radical prostatectomy for prostate cancer (PCa). Optical imaging in near-infrared window II (NIR-II) is a promising technology for intraoperative guidance, whereas there is no available probe for PCa yet. In this article, a novel probe (PSMA-1092) bearing two prostate-specific membrane antigen (PSMA) binding motifs was developed, displaying excellent optical properties (λmax = 1092 nm) and ultrahigh affinity (Ki = 80 pM) toward PSMA. The tumor was visualized with high resolution (tissue-to-normal tissue ratio = 7.62 ± 1.05) and clear margin by NIR-II imaging using PSMA-1092 in a mouse model. During the tumor resection, residual tumors missed by visible inspection were detected by the real-time imaging. Overall, PSMA-1092 displayed excellent performance in delineating the tumor margin and detecting residual tumors, demonstrating promising potential for precise PCa tumor resection in clinical practice.
Insights
A new near-infrared probe, PSMA-1092, enables precise visualization of prostate cancer (PCa) tumors. This optical imaging tool aids surgeons in identifying and resecting tumors with greater accuracy during radical prostatectomy.
Area of Science:
- Biomedical Optics
- Molecular Imaging
- Oncology
Background:
- Radical prostatectomy for prostate cancer (PCa) faces challenges due to complex anatomy, hindering precise tumor resection.
- Near-infrared window II (NIR-II) optical imaging offers potential for intraoperative guidance, but lacks specific probes for PCa.
Purpose of the Study:
- To develop and evaluate a novel NIR-II optical imaging probe for precise PCa tumor delineation and resection.
Main Methods:
- A novel probe, PSMA-1092, was designed with two prostate-specific membrane antigen (PSMA) binding motifs.
- The probe exhibited excellent optical properties (λmax = 1092 nm) and high affinity (Ki = 80 pM) for PSMA.
- NIR-II imaging using PSMA-1092 was performed in a mouse model to visualize PCa tumors.
Main Results:
- PSMA-1092 enabled high-resolution visualization of PCa tumors with a significant tumor-to-normal tissue ratio (7.62 ± 1.05).
- Clear tumor margins were delineated, and residual tumors missed by visual inspection were detected in real-time during simulated resection.
- The probe demonstrated excellent performance in identifying tumor boundaries and residual disease.
Conclusions:
- PSMA-1092 shows significant promise as an intraoperative imaging agent for precise PCa tumor resection.
- This novel probe could improve surgical outcomes by enhancing tumor margin identification and reducing the risk of residual disease.

