188Re labeled glyco-ligand OCTAM accurate estimate the remnant liver function in mouse model with schistosoma infection

Objectives New accurate non invasive means to estimate the remnant liver function are needed and can be useful to management decisions of chronic liver diseases.

Methods We developed OCTAM for binding residual liver asialoglycoprotein receptor (ASGPR) and are available for candidate drug in the testing of clinical liver function. This compound had been served as a nuclear medicine imaging agent to assist the affinity to hepatocytes in vitro. Then a SPECT/CT fusion imaging and biodistribution method was performed further to score the levels of liver remnant function in mice models with different schistosomal infection stages.

Results The results revealed that OCTAM as a specific ASGPR ligand competitive inhibited anti-ASGPR antibody attachment to hepatocytes. The competition efficiency of OCTAM was significant higher than other galactosyl ligands. In the fused Micro-SPECT/CT images of normal mice revealed strong liver uptake and continued retention there until 48hr. However, serial images of mice with schistosoma infection showed the retention of 188Re-OCTAM uptake were reverse correlated with both the stages and grades of infection. The similar results were observed in evaluating the biodistribution of 188Re-OCTAM to mice with the same conditions. The pathological analysis demonstrated that the gradually accumulated liver injury which caused by infection significantly influenced the uptake of 188Re-OCTAM and the hepatic ASGPR expression diminished in the chronic infection stage.

Conclusions Overall, this study has revealed that 188Re-OCTAM has good characteristic for liver accumulation and may be potential to serve as a functional imagine agent for liver cells. Furthermore, our study is helpful for development of drugs in future on hepatic function diagnosis of chronic liver diseases