The initial study of 99mTc-3PRGD2 molecular imaging targeting integrin αvβ3 in evaluation of liver injury
ZHANG Xin1, XIN Jun1, ZHAO Zhou-she2, CAO Li1, SHI Yu1, GUO Qi-yong1
1. Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China;2. Health Care System, GE China, Beijing 100176, China
Abstract：Objective: To evaluate the application of molecular imaging using 99mTc-3PRGD2 targeting integrin αvβ3 for diagnosis of liver injury by comparing the imaging difference between the rats with liver injury and the control ones. Methods: Six thioacetamide-induced liver injury rat models and 6 control rats were used. All the rats after satisfied anesthesia were performed whole-body planar dynamic scintigraphy immediately after the injection of 99mTc-3PRGD2 through the tail vein. The region of interest(ROI) with an area of 20 pixels was positioned in the region of liver and heart for each rat, and the liver-to-heart ratios(L/H) at 1, 5, 10, 15, 30, 45, 60, 75 and 90 min were calculated. The difference of L/H at each time point between the two groups was compared by Mann-Whitney U test, and receiver operating characteristic curve(ROC curve) was used to calculate the cutoff value with the biggest Youden’s index and the corresponding sensitivity and specificity. The liver tissue was harvested after execution and performed HE and Sirius red staining, as well as immunohistochemistry of integrin αvβ3. Results: L/H of the liver-injured group at all the time points were bigger than those of the control group, however only the difference between the two groups at 30 min post-injection of 99mTc-3PRGD2 was statistically significant(P＜0.05). The area under the curve(AUC) was 0.917, and the cutoff value was 1.58 with the Youden’s index 0.883, the sensitivity 100% and the specificity 88.3%. A large amount of ballooning degeneration liver cells in the liver-injured group was observed on the HE and Sirius red staining liver sections without apparent deposition of fibrosis(Ishak stage score=0 or 1). The diffusely positive expression of integrin αvβ3 was observed in the liver-injured group, and no positive expression was observed in the control group. Conclusion: Molecular imaging using 99mTc-3PRGD2 targeting integrin αvβ3 may be a sensitive and non-invasive method for the diagnosis of liver injury and early-stage liver fibrosis by evaluating the increased expression of integrin αvβ3, and the optimal time point for imaging is 30 min post-injection.
2014, Vol. 25 
