Evaluation of Tc-3PRGD integrin receptor imaging in hepatocellular carcinoma tumour-bearing mice: comparison with F-FDG metabolic imaging.

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.