Radiosynthesis and biological evaluation of an fluorine-18 labeled galactose derivative [18F]FPGal for imaging the hepatic asialoglycoprotein receptor. Issue 12 (15th June 2020)

• Record Type: Journal Article
• Authors: Sun, Penghui; Zhu, Yun; Han, Yanjiang; Hu, Kongzhen; Huang, Shun; Wang, Meng; Wu, Hubing; Tang, Ganghua
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 12(2020)
• Publication Date: 2020-06-15
• Subjects: [18F]FPGal -- ASGPR -- Liver function imaging agent -- PET imaging -- Click chemistry; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127187
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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. Given its hepatic distribution, the asialoglycoprotein receptor can be targeted by positron imaging agents to study liver function using PET imaging. In this study, the positron imaging agent [ 18 F]FPGal was designed to specifically target hepatic asialoglycoprotein receptor and its effectiveness was assessed in in vitro and in vivo models. The radiosynthesis of [ 18 F]FPGal required 50 min with total radiochemical yields of [ 18 F]FPGal from [ 18 F]fluoride as 10% (corrected radiochemical yield). The Kd of [ 18 F]FPGal to ASGPR in HepG2 cells was 1.99 ± 0.05 mM. Uptake values of 0.55% were observed within 30 min of incubation with HepG2 cells, which could be blocked by 200 mM d (+)-galactose (<0.1%). In vivo biodistribution analysis showed that the liver accumulation of [ 18 F]FPGal at 30 min was 4.47 ± 0.96% ID/g in normal mice compared to 1.33 ± 0.07% ID/g in hepatic fibrotic mice (P < 0.01). Reduced uptake in the hepatic fibrosis mouse models was confirmed through PET/CT images at 30 min. Compared to normal mice, the standard uptake value (SUV) in the hepatic fibrosis mice was significantly lower when assessed through dynamic data collection for 1 h. Therefore, [ 18 F]FPGal is a feasible PET probe that provide insight into ASGPR related liver disease.