精子蛋白17靶向的小鼠肿瘤近红外荧光成像

目的人精子蛋白17(human sperm protein 17,Sp17)异常表达在一些恶性肿瘤细胞,可被用作肿瘤特异性分子诊断和治疗的靶点。文中将抗Sp17单克隆抗体与近红外染料偶联,制成高亲和力探针,用近红外成像技术对活体动物肿瘤靶点进行确认。方法用免疫组化技术证明,Sp17在肝细胞癌细胞系SMMC-7721及裸鼠皮下移植瘤组织高水平异常表达。将近红外染料吲哚花箐素衍生物(ICG-Der-02)与抗Sp17单克隆抗体(anti-Sp17 mAb)偶联,获得特异性探针。静脉注射至荷瘤小鼠体内,用光学成像系统进行活体实时肿瘤显像。结果 anti-Sp17-ICG-Der-02探针进入动物体内后,快速聚集到肿瘤部位,发出强烈的荧光信号。随着未结合染料逐渐排出体外,动物肝、肾等内脏器官的非特异荧光信号消褪,清晰显示出肿瘤的部位及大小,且可以持续至少7d。结论高亲和力探针anti-Sp17-ICG-Der-02对体内肿瘤特异性诊断有潜在应用价值。

Sperm protein 17 targeted near-infrared fluorescence imaging of tumor in mice

Objective Human sperm protein 17(Sp17) is aberrantly expressed in some cancers,and can be used as a target for specific molecular diagnosis and treatment of these malignancies.The purpose of this study is to identify tumors in mice with a high-affinity probe consisting of a near-infrared(NIR) and the specific monoclonal antibody against Sp17(anti-Sp17-mab).Methods We used immunohistochemistry to identify the highly abnormal expression of Sp17 in the hepatocellular carcinoma cell line and tumor xenografts in mice.By coupling a NIR fluorescent(NIRF) cyanine dye(indocyanine green derivative 2,ICG-Der-02) to anti-Sp17-mab,we designed a bio-optical high-affinity fluorescent probe anti-Sp17-ICG-Der-02,which was injected into tumor-bearing nude mice through the caudal vein for evaluating its tumor-targeting effect by the near infrared imaging system.Results The overexpression of Sp17 was demonstrated on the surface of the hepatocellular carcinoma cell line SMMC-7721.Anti-Sp17-ICG-Der-02 with immuno-activity was successfully synthesized.The immuno-activity and photo stability of anti-Sp17-ICG-Der-02 exhibited a high targeting capability in Sp17 expressing tumor models(SMMC-7721),and its accumulation in tumors lasted for at least 7 days.Conclusion The high-affinity proble anti-Sp17-ICG-Der-02 has a potential application value for the specific diagnosis of tumor in vivo.