99Tcm-3PRGD2SPECT显像用于胰腺癌荷瘤裸鼠动物实验及临床转化研究

99Tc m-3PRGD2for Integrin Receptor Imaging of Pancreatic Cancer:Experimental Study on Tumor Bearing Nude Mice and Clinical Transformation Research

本工作探讨了新型示踪剂99 Tcm-HYNIC-3PEG4-E[c(RGDfK)]2(99 Tcm-3PRGD2)用于胰腺癌的诊断价值及临床转化可行性。用免疫组化实验测定PANC-1胰腺癌细胞以及肿瘤组织中的整合素αvβ3的表达。将PANC-1胰腺癌细胞种植于BALB/c裸鼠肩部,建立合格的动物模型。以联肼尼克酰胺(HYNIC)作为双功能连接剂,采用无亚锡一步法制备99 Tcm-3PRGD2。在0.5~6.0h,每隔0.5h行一次荷瘤鼠99 Tcm-3PRGD2全身平面显像,观察全身分布情况,于肿瘤及健侧勾画感兴趣区(ROI,region of interest),计算肿瘤与本底(T/NT)的比值。对6例胰腺肿瘤患者行99 Tcm-3PRGD2单光子发射的计算机断层显像(SPECT),评估对胰腺癌的检出率。结果表明:PANC-1胰腺癌细胞以及肿瘤组织中高表达整合素αvβ3。99 Tcm-3PRGD2标记率大于99%。荷瘤鼠显像显示肿瘤对示踪剂摄取好,0.5h时即可见肿瘤显影,1.5h时T/NT达最大值,6.0h时肿瘤仍可清晰显示。99 Tcm-3PRGD2SPECT显像可检出6例患者的胰腺肿瘤原发灶和肝转移灶,检出率为100%。99 Tcm-3PRGD2是一种安全有效的示踪剂,特异性结合整合素αvβ3,99 Tcm-3PRGD2SPECT对胰腺癌的临床诊断具有潜在的应用前景。

To evaluate an integrin imaging approach based on single photon emission computed tomography(SPECT)by using a technetium-99m(99 Tcm)labeled dimeric cyclic arginineglycine-aspartic acid(RGD)analogue(3PRGD2)as the tracer to target the integrinαvβ3 expressed pancreatic cancer.PANC-1pancreatic cancer cells and tumor tissues were stained with integrinαvβ3to find if it is operatively expressed.PANC-1pancreatic cancer cells were implanted into the shoulder of BALB/C nude mice to establish a qualified animal model.99 Tcm-3PRGD2 was prepared with hydrazine nicotinamide(HYNIC)as a dual functional linker.99 Tcm-3PRGD2whole body planar imaging was performed every 0.5hours to observe the distribution of the whole body.ROIs(regions of interest)were drawn on the tumor and the healthy side,and the ratios of tumor to background were calculated.99 Tcm-3PRGD2 SPECT was performed in 6patients with pancreatic tumor to evaluate the detection efficiency of pancreatic cancer.Integrinαvβ3is highly expressed in PANC-1pancreatic cancer cells and tumor tissues.The labeling rate of 99 Tcm-3PRGD2is more than 99%.The imaging of tumor bearing mice show that the tumor has a high uptake of the tracer,and the tumor can be seen in 0.5hp.i.,the T/NT reachs the maximum value in 1.5hp.i.,and the tumor can be clearly displayed in 6.0hours.99 Tcm-3PRGD2SPECT can detect primary pancreatic lesions and liver metastases in 6patients,with a detection rate of 100%.99 Tcm-3PRGD2imaging is sensitive for the detection of pancreatic cancer,meriting further investigation of 99 Tcm-3PRGD2 as a novel clinical tracer for integrin receptor imaging.