Development of a novel pet tracer 68GA-NOTA-KS for evaluation of hepatic function in animal models of liver fibrosis

초록

Background and Aims: The preoperative assessment of hepatic function is a crucial factor for successful liver surgery to reduce postoperative mortality and morbidity. However, conventional methods including the Child-Pugh classification, the model for end-stage liver disease (MELD), and the indocyanine green clearance are the indirect methods of measuring hepatic function, which often lead to inaccurate assessment. Asialoglycoprotein receptors are expressed on normal hepatocytes of mammals and a novel synthetic compound KS was designed to bind specifically to asialoglycoprotein receptors. Thus, 68Ga-labeled KS could be suitable for visualization of asialoglycoprotein receptors in the liver by using positron emission tomography (PET) and could directly reflect the hepatic function. Here, we investigate whether a novel PET tracer 68Ga-labeld KS could reflect the hepatic function in rats with liver fibrosis. Methods: Synthesized KS was conjugated with 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-NOTA) and labeled with 68Ga. Liver fibrosis animal models were induced by an intraperitoneal injection of thioacetamide (300 mg/kg) three times a week for 4 weeks using the male Sprague-Dawley rat. Images were acquired after injection of 68Ga-NOTA-KS in the rat tail vein before sacrifice. The liver uptake value (LUV) of 68Ga-NOTA-KS was calculated as the whole liver uptake divided by the heart uptake. Results: Functional hepatocyte imaging was successfully visualized by using 68Ga-NOTA-KS PET/CT in live animals. Furthermore, LUV of 68Ga-NOTA-KS was significantly decreased in rats with liver fibrosis, compared to normal rats. Conclusions: 68Ga-NOTA-KS PET/CT could reflect the hepatic function in liver fibrosis rat model. Thus, LUV assessed by 68Ga-NOTA-KS PET/CT could serve as a direct surrogate marker of hepatic function.