Biodistribution of (99m) Tc-Lactosylated Serum Albumin in Mice with Diethylnitrosamine or Thiacetamide Induced Liver Injury

Whang, Jae Seok; Ahn, Byeong Cheol; Sung, Young Ok; Seo, Ji Hyoung; Bae, Jin Ho; Jeong, Shin Young; Yoo, Jung Soo; Jeong, Jae Min; Lee, Jaetae; Lee, Kyu Bo

Abstract

PURPOSE
Tc-99m labeled diethylenetriaminepentaacetic acid (DTPA) -coupled galactosylated human serum albumin (GSA) is a currently used imaging agent for asialoglycoprotein receptor (ASGPR) of the liver, but, it has several shortcomings. Recently a new ASGPR imaging agent, (99m) Tc-lactosylated human serum albumin (LSA), with simple labeling procedure, high labeling efficiency, high stability was developed. In order to assess the feasibility of the (99m) Tc-LSA as a ASGPR imaging radiopharmaceuticals, we performed biodistribution study of the tracer in liver injured mice model and the results were compared with histolgic data. MATERIALS AND METHODS: To induce hepatic damage in ICR mice, diethylnitrosamine (DEN) (60 mg/kg/week X 5 time, low dose or 180 mg/kg/week X 2 times, high dose) and thioacetamide (TAA) (50 mg/kg X 1 time) were administrated intraperitoneally. Degree of liver damage was evaluated by tissue hematoxilin-eosin stain, and expression of asialoglycoprotein receptor (ASGPR) was assessed by immunohistochemistry using ASGPR antibody. (99m) Tc-LSA was intravenously administrated via tail vein in DEN or TAA treated mice, and biodistribution study of the tracer was also performed. RESULTS: DEN treated mice showed ballooning of hepatocyte and inflammatory cell infiltration in low dose group and severe hapatocyte necrosis in high dose group, and low dose group showed higher ASGPR staining than control mice in immunohistochemical staining. TAA treated mice showed severe hepatic necrosis. (99m) Tc-LSA Biodistribution study showed that mice with hepatic necrosis induced by high dose DEN or TAA revealed higher blood activity and lower liver activity than control mice, due to slow clearance of the tracer by the liver. The degree of liver uptake was inversely correlated with the degree of histologic liver damage. But low dose DEN treated mice with mild hepatic injury showed normal blood clearance and hepatic activity, partly due to overexpression of ASGPR in mice with mild degree hepatic injury. CONCLUSION: Liver uptake of (99m) Tc-LSA was inversely correlated with degree of histologic hepatic injury in DEN and TAA treated mice. These results support that (99m) Tc-LSA can be used to evaluate the liver status in liver disease patients.