Evaluation of liver fibrosis by SPECT/CT imaging of asialoglycoprotein receptor with 99mTc-galactose derivative in mouse models

1595 Objectives Asialoglycoprotein receptors (ASGPR), with high-affinity for galactose residues, are located on the hepatocyte membrane. Noninvasive quantification of the expression of ASGPR could help assess the liver function and diagnose the liver diseases. This study developed 99mTc-labeled monomeric and dimeric galactose derivatives (99mTc-MGal and 99mTc-DGal) as SPECT probes for evaluation of ASGPR density in normal and liver fibrosis animal models. Methods 99mTc-MGal and 99mTc-DGal were prepared via a multi-step synthesis (total synthesis yield of precursor were 14.3% and 7.3%, respectively; the radiochemical purities were both >98%). Liver fibrosis in C57BL/6 mouse was induced after treated with 12 doses of dimethylnitrosamine, and was evidenced by histological examination. The biodistribution study and dynamic SPECT/CT imaging of 99mTc-MGal and 99mTc-DGal were performed in normal and fibrosis mice. Results Though high liver uptakes were observed in both fibrosis and normal mice at 5 min after injection of 99mTc-MGal and 99mTc-DGal, specific liver uptake (liver-to-blood ratio) at 5 min and 30 min (P Conclusions In this study, 99mTc-MGal and 99mTc-DGal, with specific binding to ASGPR, were demonstrated as promising SPECT probes that can in vivo distinguish the fibrosis liver from the normal. 99mTc-MGal and 99mTc-DGal might have potential for diagnosing the ASGP-related liver diseases