人前列腺癌靶向超声造影剂对荷瘤裸鼠靶向显像的研究

The targeted ultrasound contrast imaging for human prostatic carcinoma borne by nude mice：an experimental study

目的：探讨携前列腺特异性膜抗原（PSMA）抗体和携血管内皮生长因子（VEGF）抗体的靶向超声造影剂对荷人前列腺癌裸鼠的特异增强显像效果。方法：人前列腺癌细胞株LNCaP体外无菌条件下培养传代，BALB／c-nu雄性裸鼠皮下接种，建立荷人前列腺癌裸鼠动物模型。分别经荷瘤裸鼠尾静脉推注普通造影剂和携PSMA抗体及携VEGF抗体的靶向造影剂12min后采用能量多普勒成像，测量并计算肿瘤截面内血流信号所占的面积比，并分析比较普通造影剂和靶向造影剂对前列腺癌组织能量多普勒信号的增强效果。结果：成功建立了荷人前列腺癌裸鼠动物模型，推注携带VEGF抗体的靶向造影剂超声造影后行能量多普勒显像，可见前列腺癌组织能量多普勒信号显著增强，与普通造影剂和携带PSMA抗体的靶向造影剂相比较，差异有统计学意义（P〈0．01）。结论：VEGF抗体介导的靶向超声造影剂在体内可以有效特异性地与前列腺肿瘤新生血管内皮细胞结合，可作为诊断前列腺癌的靶向造影剂。能量多普勒延迟显像能有效显示靶向造影后肿瘤组织内的能量多普勒增强信号。

Objective To investigate the specific enhancement effects of two sorts of human prostatic carcinoma-targeted ultrasound contrast agent using anti-PSMA antibody and anti-VEGF antibody as ligand respectively on human prostatic carcinoma（PCa） borne by nude mice. Methods Tumor cell line LNCaP of human PCa was cultivated,passaged in vitro and inoculated subcutaneously into male nude mice to establish tumor bearing nude mice model of human PCa. Twenty four nude mice bearing tumor were divided into 3 groups randomly. Common microbubbles and targeted microbubbles carrying anti-PSMA antibody and anti- VEGF antibody were injected respectively. After a delay of 12 min without scanning, the tumors were examined using power Doppler imaging. The blood flow area ratio（BFAR） was measured and calculated,and the BFAR in all groups were analyzed and compared. Results The tumor PCa bearing nude mice model was established successfully. Applying power Doppler imaging, the signal in the tumor was enhanced markedly after the targeted microbubbles carrying anti-VEGF antibody was injected, and the BFAR in VEGF group was significantly higher than those in common group and PSMA group （ P 〈0.01 ）. Conclusions The microbubbles carring anti-VEGF antibody can retain in human prostatic cancer tissue in vivo specifically and effectively,which can be applied to diagnose prostatic cancer as a targeted contrast agent. Delayed power Doppler imaging is a good mode to show the enhanced sigal of tumor after targeting contrast.