More important, after intravenous injection FAM-cRGD was found to accumulate in fibrotic livers and the accumulation amount was increased with the progression of liver fibrosis and reduced with the regression of liver fibrosis (Supporting Fig. 2). Taken together, these results provide convincing evidence that visualizing hepatic expression of integrin αvβ3 could distinguish HSC activity in different stages of liver fibrosis. In the organ distribution study of 125I-cRGD, we found that the

predominant excretion pathway of synthetic cRGD was through kidneys and hepatobiliary routes in both control and fibrotic rats, and that there was minimal accumulation in other organs 45 minutes after intravenous administration,

indicating that the in vivo retention of radionuclide was minimal. The hepatic accumulation of 125I-cRGD in rats with liver fibrosis was higher than that Alisertib order in control rats and administration of excessive unlabeled cRGD reduced 125I-cRGD accumulation in fibrotic livers, especially in advanced fibrosis, which indicated that the accumulation of 125I-cRGD in fibrotic liver was interfered by competing for the receptors with unlabeled cRGD. Given the fact that synthesized cRGD was mainly excreted through the renal and hepatobiliary routes, the image of 99mTc-labeled cRGD in livers by SPECT modality would inevitably be interfered by the shadow of the kidneys, especially the right kidney

neighboring the liver. In normal rats, the highest MCE公司 basal expression of β3 integrin mRNA was found in liver and less was found in heart.17 In our biodistribution Selleckchem Alectinib study, accumulation of 125I-cRGD in the heart did not change markedly in fibrotic rats compared to control rats. Therefore, the accumulation of cRGD in the heart was relatively invariant in fibrotic rats in comparison to control rats, and MRAR could be considered a valuable index to reflect the relative binding amount of 99mTc-labeled cRGD in the liver. MRAR was significantly increased in rats with liver fibrosis compared to that in control rats. It was the highest in the rats with advanced fibrosis, whereas the biodistribution study showed that there was the least 125I-cRGD accumulation in the kidneys from these rats with advanced fibrosis. Furthermore, in the organ distribution study it was evident that there was no significant difference in 125I-cRGD accumulation in kidneys between the rats with mild fibrosis and the control rats, whereas MRAR in the mild fibrosis was significantly higher than that in normal livers. Based on these findings, we overcame the disturbance of renal visualization to hepatic visualization in imaging integrin αvβ3 expression with SPECT imaging by comparing MRAR in rats, although further studies are needed to further improve this imaging modality.