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EJNMMI Research
Published in: EJNMMI Research 1/2020

01-12-2020 | Fatty Liver | Original research

Quantitative evaluation of hepatic integrin αvβ3 expression by positron emission tomography imaging using 18F-FPP-RGD2 in rats with non-alcoholic steatohepatitis

Authors: Shuichi Hiroyama, Takemi Rokugawa, Miwa Ito, Hitoshi Iimori, Ippei Morita, Hiroki Maeda, Kae Fujisawa, Keiko Matsunaga, Eku Shimosegawa, Kohji Abe

Published in: EJNMMI Research | Issue 1/2020

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Abstract

Background

Integrin αvβ3, which are expressed by activated hepatic stellate cells in non-alcoholic steatohepatitis (NASH), play an important role in the fibrosis. Recently, we reported that an RGD peptide positron emission tomography (PET) probe is useful as a predictor of hepatic fibrosis. Kinetic analysis of the RGD PET probe has been performed in tumours, but not in hepatic fibrosis. Therefore, we aimed to quantify hepatic integrin αvβ3 in a model of NASH by kinetic analysis using 18F-FPP-RGD2, an integrin αvβ3 PET probe.

Methods

18F-FPP-RGD2 PET/CT scans were performed in control and NASH rats. Tissue kinetic analyses were performed using a one-tissue, two-compartment (1T2C) and a two-tissue, three-compartment (2T3C) model using an image-derived input function (IDIF) for the left ventricle. We then conducted correlation analysis between standard uptake values (SUVs) or volume of distribution (VT), evaluated using compartment kinetic analysis and integrin αv or β3 protein expression.

Results

Biochemical and histological evaluation confirmed the development of NASH rats. Integrin αvβ3 protein expression and hepatic SUV were higher in NASH- than normal rats. The hepatic activity of 18F-FPP-RGD2 peaked rapidly after administration and then gradually decreased, whereas left ventricular activity rapidly disappeared. The 2T3C model was found to be preferable for 18F-FPP-RGD2 kinetic analysis in the liver. The VT (IDIF) for 18F-FPP-RGD2, calculated using the 2T3C model, was significantly higher in NASH- than normal rats and correlated strongly with hepatic integrin αv and β3 protein expression. The strengths of these correlations were similar to those between SUV60–90 min and hepatic integrin αv or β3 protein expression.

Conclusions

We have demonstrated that the VT (IDIF) of 18F-FPP-RGD2, calculated using kinetic modelling, positively correlates with integrin αv and β3 protein in the liver of NASH rats. These findings suggest that hepatic VT (IDIF) provides a quantitative assessment of integrin αvβ3 protein in liver.
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Metadata
Title
Quantitative evaluation of hepatic integrin αvβ3 expression by positron emission tomography imaging using 18F-FPP-RGD2 in rats with non-alcoholic steatohepatitis
Authors
Shuichi Hiroyama
Takemi Rokugawa
Miwa Ito
Hitoshi Iimori
Ippei Morita
Hiroki Maeda
Kae Fujisawa
Keiko Matsunaga
Eku Shimosegawa
Kohji Abe
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-020-00704-3

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