基于CDCP1纳米液滴造影剂靶向超声成像在前列腺癌侵袭性及疗效评估的研究

前列腺癌的侵袭性和疗效评估对提高前列腺癌治愈率具有十分重要作用，目前临床尚缺乏一种能早期、准确、可重复评估前列腺癌侵袭性和疗效的无创方法。我们的前期研究证实靶向超声造影成像可反映前列腺癌组织的蛋白表达状况。本项目在此基础上，以前列腺上皮细胞为靶点，采用乳化溶剂挥发法制备针对CDCP1抗原的纳米液滴靶向造影剂，通过建立PC-3、DU145和LNCaP人前列腺癌裸鼠皮下移植模型，应用Western blot、激光共聚焦显微镜、免疫组化分析CDCP1的表达情况和造影剂体内靶向结合情况，利用超声定量分析软件分析靶向造影剂对评估前列腺癌侵袭性的作用。在完成PC-3前列腺癌裸鼠移植瘤的冷冻和射频治疗后，应用靶向造影剂超声造影成像及其分析软件进行疗效评估，与病理为对照研究创建靶向超声造影的前列腺癌疗效评估方法。为临床通过无创的超声影像方法获得前列腺癌肿瘤的生物特性及治疗后变化机制奠定基础。

The assessment of the aggressiveness and therapeutic response of prostate cancer plays a crucial role in treatment decision and prognosis prediction. However, a non-invasive diagnostic tool which could accurately assess the aggressiveness and therapeutic response of prostate cancer is still not available in clinical. Our preliminary study demonstrated that targeted contrast enhanced ultrasound could improve prostate cancer detection by imaging tumor-specific biomarkers. Based on the preliminary findings,this study employs solvent emulsion/evaporation method to fabricate nanodroplet contrast agents targeting CDCP1 antigen expressed on prostate cancer cell membrane. Prostate cancer xenograft models with different aggressiveness are established using PC-3, DU145 and LNCaP cell lines. The in vivo targeting ability of nanodroplet contrast agents are studied by laser scanning confocal microscopy, immunohistochemistry and Western-blotting. Quantitative analysis software is employed for the evaluation of nanodroplet contrast agents in imaging prostate cancer aggressiveness. After cryoablation and radiofrequency ablation of PC-3 prostate cancer xenograft model, the therapeutic response is imaged using nanodroplet contrast agents. The treatment evaluation method is further established with quantitative analysis in comparison with pathologic findings. Our study will lay the groundwork for ultrasonic imaging of the biologic behavior and therapeutic response of prostate cancer.