RETRACTED: Radiosynthesis and biological evaluation of fluorine-18 labeled N-acetylgalactosamine derivative [18F]FPGalNAc for PET imaging of asialoglycoprotein receptor-positive tumors

Abstract

The asialoglycoprotein receptor(ASGPR) is abundantly expressed on the surface of hepatocytes where it recognizes and endocytoses glycoproteins with galactosyl and N-acetylgalactosamine groups. ASGPR not only express on the surface of hepatocytes, but also express in several tumor cells (HepG2, A549 and HCT116). The purpose of this study was to develop a ASGPR-specific radiofluorinated ligand for positron emission tomography (PET) imaging in several tumor models. The radiosynthesis of [18F]FPGalNAc was initiated with fluorine-18 and 5-(p-toluenesulfonyl)-1-yne. The obtained 5-[18F]fluoro-1-pentyne intermediate was then reacted with 2-acetamido-2-deoxy-β-d-galactopyranosyl azide using "click chemistry" to produce the final product. The Kd of the product was determined in HepG2 cells at a range of concentrations of [18F]FPGalNAc. Cellular uptake and blocking experiments were also performed. In vivo biodistribution studies were performed in nude mice bearing HCT116 tumor and micro positron emission tomography/computed tomography (PET/CT) evaluations were then performed in tumor-bearing mice (HepG2, HCT116) models. The radiosynthesis of [18F]FPGalNAc required 50min with 5-6% RCY (radiochemical yield). The Kd of [18F]FPGalNAc to ASGPR in HepG2 cells was 0.25±0.02mM. Uptake values of 0.29% were observed within 30min of incubation with HepG2 cells, which could be blocked by 200mM d(+)-galactose (< 0.13%). The data of biodistribution revealed that the uptake of [18F]FPGalNAc was higher in kidneys and liver, and lower in muscle, bone and brain. In vivo micro PET studies, both HCT116 and HepG2 tumors showed high uptake for [18F]FPGalNAc, the radio of tumor/muscle (T/M) was 3.7 and 3.91, respectively. In vitro assays and in vivo PET/CT imaging and biodistribution studies showed that [18F]FPGalNAc represents a promising tumor imaging agent that can provide insight into ASGPR related disease.