Radiosynthesis and biological evaluation of an fluorine-18 labeled galactose derivative [18F]FPGal for imaging the hepatic asialoglycoprotein receptor.
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 [18F]FPGal was designed to specifically target hepatic asialoglycoprotein receptor and its effectiveness was assessed in in vitro and in vivo models. The radiosynthesis of [18F]FPGal required 50 min with total radiochemical yields of [18F]FPGal from [18F]fluoride as 10% (corrected radiochemical yield). The Kd of [18F]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 [18F]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, [18F]FPGal is a feasible PET probe that provide insight into ASGPR related liver disease.
['Sun|Penghui|P|', 'Zhu|Yun|Y|', 'Han|Yanjiang|Y|', 'Hu|Kongzhen|K|', 'Huang|Shun|S|', 'Wang|Meng|M|', 'Wu|Hubing|H|', 'Tang|Ganghua|G|']
D000818:Animals D037263:Asialoglycoprotein Receptor D057930:Click Chemistry D004195:Disease Models, Animal D005462:Fluorine Radioisotopes D005690:Galactose D056945:Hep G2 Cells D006801:Humans D007553:Isotope Labeling D007700:Kinetics D008099:Liver D008103:Liver Cirrhosis D051379:Mice D000072078:Positron Emission Tomography Computed Tomography D019275:Radiopharmaceuticals D014018:Tissue Distribution
ASGPR PET imaging Click chemistry Liver function imaging agent [(18)F]FPGal