Zheng Jieling, Miao Weibing, Huang Chao, Lin Haoxue
Department of Nuclear Medicine, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Taijiang District, Fuzhou, 350005, China.
Ann Nucl Med. 2017 Jul;31(6):486-494. doi: 10.1007/s12149-017-1173-4. Epub 2017 May 4.
Our study was designed to explore the utility of Tc-HYNIC-PEG-E[PEG-c(RGDfK)] (Tc-3PRGD) for the detection of hepatocellular carcinoma (HCC) and specifically to compare the diagnostic performance of Tc-3PRGD integrin receptor imaging and 2-18-fluoro-2-deoxy-D-glucose (F-FDG) metabolic imaging in a nude mouse model.
Tc-3PRGD was synthesized using a HYNIC-3PRGD lyophilized kit with TcO labelling. The nude mouse animal model was established by subcutaneously injecting 5 × 10/ml HepG2 cells into the shoulder flank of each mouse. Biodistribution studies were performed at 0.5, 1, 2 and 4 h after intravenous administration of 0.37 MBq of Tc-3PRGD. Immunohistochemistry was performed to evaluate the expression level of integrin αvβ3 in the HCC tissues. Dynamic imaging was performed using list-mode after the administration of 55.5 MBq of Tc-3PRGD, to reconstruct the multiphase images and acquire the best initial scan time. At 8, 12, 16, 20 and 24 days after inoculation with HepG2 cells, 55.5 MBq of Tc-3PRGD and 37 MBq of F-FDG were injected successively into the nude mouse model, subsequently, simultaneous SPECT/PET imaging was performed to calculate the tumour volume and tumour uptake of Tc-3PRGD and F-FDG.
The biodistribution study first validated that the tumour uptake of Tc-3PRGD at the different time points was higher than that of all the other organs tested in the experiment, except for the kidney. Integrin αvβ3 expressed highly in early stage HCC and declined for further necrosis of the tumour tissue. Subcutaneous tumours were visualized clearly with excellent contrast under Tc-3PRGD SPECT/CT imaging, and the multiphase imaging comparison showed the tumours were prominent at 0.5 h, suggesting that the best initial scan time is 0.5 h post-injection. The comparison of the imaging results of the two methods showed that Tc-3PRGD integrin receptor imaging was more sensitive than F-FDG metabolic imaging for the detection of early stage HCC, meanwhile the tumour uptake of Tc-3PRGD was consistently higher than that of F-FDG. However, as tumour necrosis further increased in HCC tissues, the uptake of F-FDG was higher than that of Tc-3PRGD.
Our study demonstrated that Tc-3PRGD is a valuable tumour molecular probe for the detection of early stage HCC compared with F-FDG, meriting further investigation of Tc-3PRGD as a novel SPECT tracer for tumour imaging.
本研究旨在探讨锝标记的HYNIC-聚乙二醇-E[聚乙二醇-c(RGDfK)]（Tc-3PRGD）用于检测肝细胞癌（HCC）的效用，并特别比较Tc-3PRGD整合素受体成像与2-18-氟-2-脱氧-D-葡萄糖（F-FDG）代谢成像在裸鼠模型中的诊断性能。
使用含锝标记的HYNIC-3PRGD冻干试剂盒合成Tc-3PRGD。通过将5×10⁶/ml HepG2细胞皮下注射到每只小鼠的肩部侧面建立裸鼠动物模型。在静脉注射0.37 MBq的Tc-3PRGD后0.5、1、2和4小时进行生物分布研究。进行免疫组织化学以评估HCC组织中整合素αvβ3的表达水平。在注射55.5 MBq的Tc-3PRGD后使用列表模式进行动态成像，以重建多期图像并获取最佳初始扫描时间。在接种HepG2细胞后的第8、12、16、20和24天，将55.5 MBq的Tc-3PRGD和37 MBq的F-FDG先后注射到裸鼠模型中，随后进行同步SPECT/PET成像以计算肿瘤体积以及Tc-3PRGD和F-FDG的肿瘤摄取量。
生物分布研究首先证实，除肾脏外，在不同时间点Tc-3PRGD的肿瘤摄取量高于实验中测试的所有其他器官。整合素αvβ3在早期HCC中高表达，并随着肿瘤组织进一步坏死而下降。在Tc-3PRGD SPECT/CT成像下，皮下肿瘤清晰可见，对比度极佳，多期成像比较显示肿瘤在0.5小时时最为突出，表明最佳初始扫描时间为注射后0.5小时。两种方法的成像结果比较表明，Tc-3PRGD整合素受体成像在检测早期HCC方面比F-FDG代谢成像更敏感，同时Tc-3PRGD的肿瘤摄取量始终高于F-FDG。然而，随着HCC组织中肿瘤坏死进一步增加，F-FDG的摄取量高于Tc-3PRGD。
我们的研究表明，与F-FDG相比，Tc-3PRGD是一种用于检测早期HCC的有价值的肿瘤分子探针，值得进一步研究将Tc-3PRGD作为一种新型的SPECT肿瘤显像剂。
