99Tcm-3PRGD2 SPECT显像用于胰腺癌荷瘤裸鼠动物实验及临床转化研究

本工作探讨了新型示踪剂⁹⁹Tc^m-HYNIC-3PEG₄-E［c(RGDfK)］₂（⁹⁹Tc^m-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α_vβ₃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⁹⁹Tc^m-3PRGD₂。在0.5~6.0 h，每隔0.5 h行一次荷瘤鼠⁹⁹Tc^m-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99Tcm-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α_vβ₃。⁹⁹Tc^m-3PRGD2标记率大于99%。荷瘤鼠显像显示肿瘤对示踪剂摄取好，0.5 h时即可见肿瘤显影，1.5 h时T/NT达最大值，6.0 h时肿瘤仍可清晰显示。⁹⁹Tc^m-3PRGD₂ SPECT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%。⁹⁹Tc^m-3PRGD₂是一种安全有效的示踪剂，特异性结合整合素α_vβ₃，⁹⁹Tc^m-3PRGD₂ SPECT对胰腺癌的临床诊断具有潜在的应用前景。

99 Tcm-3PRGD2 for Integrin Receptor Imaging of Pancreatic Cancer:Experimental Study on Tumor Bearing Nude Mice and Clinical Transformation Research

To evaluate an integrin imaging approach based on single photon emission computed tomography(SPECT) by using a technetium-99m(⁹⁹Tc^m) labeled dimeric cyclic arginine-glycine-aspartic acid(RGD) analogue(3PRGD₂) as the tracer to target the integrin α_vβ₃ expressed pancreatic cancer. PANC-1 pancreatic cancer cells and tumor tissues were stained with integrin α_vβ₃ to find if it is operatively expressed. PANC-1 pancreatic cancer cells were implanted into the shoulder of BALB/C nude mice to establish a qualified animal model. ⁹⁹Tc^m-3PRGD₂ was prepared with hydrazine nicotinamide(HYNIC) as a dual functional linker. ⁹⁹Tc^m-3PRGD₂ whole body planar imaging was performed every 0.5 hours 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. ⁹⁹Tc^m-3PRGD₂ SPECT was performed in 6 patients with pancreatic tumor to evaluate the detection efficiency of pancreatic cancer. Integrin α_vβ₃ is highly expressed in PANC-1 pancreatic cancer cells and tumor tissues. The labeling rate of ⁹⁹Tc^m-3PRGD₂ is 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 0.5 h p.i., the T/NT reachs the maximum value in 1.5 h p.i., and the tumor can be clearly displayed in 6.0 hours. ⁹⁹Tc^m-3PRGD₂ SPECT can detect primary pancreatic lesions and liver metastases in 6 patients, with a detection rate of 100%. ⁹⁹Tc^m-3PRGD₂ imaging is sensitive for the detection of pancreatic cancer, meriting further investigation of ⁹⁹Tc^m-3PRGD₂ as a novel clinical tracer for integrin receptor imaging.