1. Radiosynthesis and biological evaluation of an fluorine-18 labeled galactose derivative [ 18 F]FPGal for imaging the hepatic asialoglycoprotein receptor.
- Author
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Sun P, Zhu Y, Han Y, Hu K, Huang S, Wang M, Wu H, and Tang G
- Subjects
- Animals, Asialoglycoprotein Receptor metabolism, Click Chemistry, Disease Models, Animal, Galactose metabolism, Hep G2 Cells, Humans, Isotope Labeling, Kinetics, Mice, Positron Emission Tomography Computed Tomography methods, Radiopharmaceuticals metabolism, Tissue Distribution, Asialoglycoprotein Receptor analysis, Fluorine Radioisotopes chemistry, Galactose chemistry, Liver metabolism, Liver Cirrhosis diagnostic imaging, Radiopharmaceuticals chemistry
- 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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