Subclassification of liver cirrhosis with molecular imaging using 99mTc-3PRGD2 targeting integrin αvβ3

Objectives Activated hepatic stellate cells (HSCs) are the main collagen-producing cells in the injured liver. Therefore, there may be some relationship between the content of hepatic collagen in the cirrhotic liver and acitivation of HSCs. In this study, we aimed to investigate the application of 99mTc-3PRGD2 imaging for liver cirrhosis substaging by studying the relationship between the liver uptake level of 99mTc-3PRGD2, which can represent activation of HSCs, and the amount of the collagen deposited.

Methods Twelve rat models of thioacetamide-induced liver cirrhosis were used, and 6 normal rats composed the control group. All the rats were performed whole-body planar static scintigraphy at 30min post-injection of 99mTc-3PRGD2 for 10min. The integrin αvβ3 binding in the liver was assessed by liver-to-heart ratios (L/H). The integrin αvβ3 specific binding of the radiotracer was assessed by co-injection of cold c(RGDyK) and 99mTc-3PRGD2. The liver tissue was harvested and performed HE and Sirius red staining, immunohistochemistry of integrin αvβ3. Liver collagen was expressed by collagen proportionate area (CPA) calculated by Image-Pro Plus 6.0 software.

Results No significant binding of 99mTc-3PRGD2 and no integrin αvβ3-positve cells were detected in the livers of control rats. The binding of 99mTc-3PRGD2 was apparently inhibited by cold c(RGDyK) in the cirrhotic liver. CPA in the cirrhotic livers ranged form 10.72% to 20.41%. L/H was increased with CPA.

Conclusions The uptake level of 99mTc-3PRGD2 is increased with the amount of collagen deposited in the cirrhotic liver. 99mTc-3PRGD2 sintigraphy, as a noninvasive method, has the potential for substaging of liver cirrhosis.