靶向PSMA新型核素探针构建与前列腺癌PET显像研究

Construction of a Novel PSMA-Targeted Radiotracer and Its Application in Prostate Cancer PET Imaging

关键词:  前列腺癌  前列腺特异性膜抗原（PSMA）  分子探针  正电子发射计算机断层扫描（PET）  18F-TTCO-SA-PSMA

Key words:  Prostate cancer  Prostate-specific membrane antigen (PSMA)  Molecular probe  Positron Emission Tomography (PET)  1?F-TTCO-SA-PSMA

摘要:

本研究基于高亲和力谷氨酸-脲基-赖氨酸（Glu-Urea-Lys）骨架，结合生物正交1?F标记策略，开发了一种新型前列腺特异性膜抗原（PSMA）靶向PET探针1?F-TTCO-SA-PSMA。该探针通过高效的点击化学标记实现高放射化学产率，并在前列腺癌模型中展现出优异的诊断性能。小动物PET/CT成像及生物分布研究表明，1?F-TTCO-SA-PSMA具有与临床金标准??Ga-PSMA-11相当的肿瘤摄取能力，同时显著降低肾脏滞留并呈现快速清除特性。相较于??Ga标记探针，1?F标记不仅延长了示踪剂的有效使用时间，其更优的正电子能量特性（Eβ????=635 keV）还提升了成像分辨率。这些优势使1?F-TTCO-SA-PSMA成为极具临床转化前景的PSMA靶向剂，其高肿瘤/背景比特性尤其适合前列腺癌微小病灶的检测，未来可进一步探索其在诊疗一体化中的应用潜力。

Abstract:

Based on the high-affinity glutamate-urea-lysine (Glu-Urea-Lys) scaffold and utilizing a bioorthogonal 1?F-labeling strategy, this study developed a novel prostate-specific membrane antigen (PSMA)-targeted PET probe, 1?F-TTCO-SA-PSMA. This probe achieved high radiochemical yield through efficient click chemistry labeling and demonstrated excellent diagnostic performance in prostate cancer models. Small-animal PET/CT imaging and biodistribution studies revealed that 1?F-TTCO-SA-PSMA possesses tumor uptake capability comparable to the clinical gold standard ??Ga-PSMA-11, while significantly reducing renal retention and exhibiting rapid clearance characteristics. Compared with ??Ga-labeled probes, the 1?F-labeling not only extends the effective usage time of the tracer but also improves imaging resolution due to its superior positron energy characteristics (Eβ????=635 keV). These advantages position 1?F-TTCO-SA-PSMA as a highly promising PSMA-targeted agent for clinical translation. Its high tumor-to-background ratio is particularly suitable for detecting small prostate cancer lesions. Future studies may further explore its potential in theranostic applications.