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Quantitative evaluation of hepatic integrin ?v?3 expression by positron emission tomography imaging using 18F-FPP-RGD2 in rats with non-alcoholic steatohepatitis.


ABSTRACT:

Background

Integrin ?v?3, 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 ?v?3 in a model of NASH by kinetic analysis using 18F-FPP-RGD2, an integrin ?v?3 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 ?v or ?3 protein expression.

Results

Biochemical and histological evaluation confirmed the development of NASH rats. Integrin ?v?3 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 ?v and ?3 protein expression. The strengths of these correlations were similar to those between SUV60-90 min and hepatic integrin ?v or ?3 protein expression.

Conclusions

We have demonstrated that the VT (IDIF) of 18F-FPP-RGD2, calculated using kinetic modelling, positively correlates with integrin ?v and ?3 protein in the liver of NASH rats. These findings suggest that hepatic VT (IDIF) provides a quantitative assessment of integrin ?v?3 protein in liver.

SUBMITTER: Hiroyama S 

PROVIDER: S-EPMC7541810 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Quantitative evaluation of hepatic integrin α<sub>v</sub>β<sub>3</sub> expression by positron emission tomography imaging using <sup>18</sup>F-FPP-RGD<sub>2</sub> in rats with non-alcoholic steatohepatitis.

Hiroyama Shuichi S   Rokugawa Takemi T   Ito Miwa M   Iimori Hitoshi H   Morita Ippei I   Maeda Hiroki H   Fujisawa Kae K   Matsunaga Keiko K   Shimosegawa Eku E   Abe Kohji K  

EJNMMI research 20201007 1


<h4>Background</h4>Integrin α<sub>v</sub>β<sub>3</sub>, 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 α<sub>v</sub>β<sub>3</sub> in a  ...[more]

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