Ghrelin类似物探针在活体前列腺癌模型中的分子影像学研究

Prostate cancer is a common malignant tumor in male, and the incidence of prostate cancer in Chinese population is rising. Extensive prostate-specific antigen screening and invasive prostate biopsy have benefited patients by reducing cancer-specific mortality, but also led to the over-treatment of minimally invasive prostate cancer. Focusing on this dilemma in clinical decision, this project will use GHSR as a targeted receptor, which is highly expressed in human prostate cancer, for the molecular Imaging in prostate cancer. Based on the structure of GHSR's endogenous ligand Ghrelin, an analogue probe will be designed and synthesized, and further used in in vivo optical imaging in prostate cancer xenograft models. The probe's ability to identify invasive prostate will also be evaluated. This project is designed to explore the application of Ghrelin and GHSR in the molecular imaging diagnosis of human prostate cancer: the GHSR-specific contrast agent may provide the imaging information as well as the invasiveness information in prostate cancer, to assist clinicians make appropriate treatment decisions, avoiding repeated prostate biopsy, and ultimately strike a balance between the early control and over-treatment in prostate cancer.

前列腺癌是男性生殖系统常见的恶性肿瘤，并且中国人群的前列腺癌发病率正在持续上升。广泛开展前列腺特异性抗原筛查和有创性前列腺穿刺活检，在通过早期诊断降低前列腺癌的特异性死亡率的同时，也导致了对低风险性前列腺癌患者的过度治疗。针对这一临床决策问题，本项目将以人类前列腺癌中高表达的GHSR为靶向受体，根据其内源性配体Ghrelin结构设计合成Ghrelin类似物探针，于活体前列腺癌模型中进行探针的成像研究，并进一步评价探针对前列腺癌恶性程度的鉴别能力，以探索Ghrelin及GHSR在人类前列腺癌分子影像学诊断中的应用前景：针对GHSR的特异性Ghrelin造影剂在提供前列腺癌影像学信息的同时，能够提供生物学信息，协助临床决策者在避免反复前列腺穿刺活检的条件下，对肿瘤恶性程度进行有效评估并做出相应治疗决策，最终在前列腺癌的早期控制与过度治疗之间取得平衡。