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

2020 ◽  
Author(s):  
Shuichi Hiroyama ◽  
Takemi Rokugawa ◽  
Miwa Ito ◽  
Hitoshi Iimori ◽  
Ippei Morita ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Protein Expression ◽  
Kinetic Analysis ◽  
Hepatic Fibrosis ◽  
Kinetic Modelling ◽  
Left Ventricular ◽  
Emission Tomography ◽  
Histological Evaluation ◽  
Alcoholic Steatohepatitis ◽  
Positron Emission

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.

scholarly journals ​Quantitative Evaluation of Hepatic Integrin Αvβ3 Expression by Positron-emission Tomography Imaging Using 18F-FPP-RGD2 in Rats With Non-alcoholic Steatohepatitis

2020 ◽  
Author(s):  
Shuichi Hiroyama ◽  
Takemi Rokugawa ◽  
Miwa Ito ◽  
Hitoshi Iimori ◽  
Ippei Morita ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Protein Expression ◽  
Kinetic Analysis ◽  
Hepatic Fibrosis ◽  
Kinetic Modelling ◽  
Left Ventricular ◽  
Emission Tomography ◽  
Histological Evaluation ◽  
Alcoholic Steatohepatitis ◽  
Positron Emission

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.

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

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shuichi Hiroyama ◽  
Takemi Rokugawa ◽  
Miwa Ito ◽  
Hitoshi Iimori ◽  
Ippei Morita ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Protein Expression ◽  
Kinetic Analysis ◽  
Hepatic Fibrosis ◽  
Kinetic Modelling ◽  
Left Ventricular ◽  
Emission Tomography ◽  
Histological Evaluation ◽  
Alcoholic Steatohepatitis ◽  
Positron Emission

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.

P250 Evaluation of coronary endothelial dysfunction by positron emission tomography: does gender make a difference

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
A Aljizeeri ◽  
M Alali Alfaris ◽  
D Ahmed ◽  
J Farea ◽  
A Elneama ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Myocardial Blood Flow ◽  
Left Ventricular ◽  
Hazard Ratio ◽  
Emission Tomography ◽  
Left Ventricular Ejection ◽  
Positron Emission ◽  
High Calcium

Abstract Funding Acknowledgements None Introduction Endothelial dysfunction (ED) manifested as abnormality of coronary microvasculature is associated with poor prognosis in patients presenting with chest pain. ED can be noninvasively evaluated by assessment of coronary flow reserve with positron emission tomography (PET). Studies directly comparing ED in men and women are limited. The aim of this study is to compare gender differences in ED as measured by CFR on PET myocardial perfusion imaging. Methods All the consecutive patients referred to PET-MPI between May 2011 and June 2018 were reviewed. Patient without known CAD who had normal perfusion were included in the analysis. Patient with abnormal electrocardiogram, significant transient ischemic dilatation, low left ventricular ejection fraction and high calcium score (>1000 AU) and renal failure were excluded. CFR is calculated as the ratio of stress/rest myocardial blood flow. CFR < 2 was considered as abnormal indicating the presence of ED. Results 1711 patients were included in the analysis (mean age 60.2 ± 10 year, 68% females). Females were older and had higher BMI and diabetes (DM). Both resting and peak myocardial blood flow (MBF) was higher in females (1.16 vs 1.02 (p < 0.0001)) and 3.26 vs 2.9 (p < 0.001)0 respectively.  Around 68% of males had abnormal CFR (<2) compared to 63% of females (p = 0.05). After adjusting for the confounders, female gender was associated with higher peak MBF (Hazard ratio 0.29, 95% CI 0.19 –0.40, p < 0.001) and lower chance of having ED (Hazard ratio -0.15, 95% CI -0.29 - -0.005, p = 0.049) Conclusions Endothelial dysfunction as measured noninvasively by CFR on PET is prevalent among both sexes. Higher level of peak MBF in females may call for a different cut-off for abnormal CFR in women. Outcome studies are required to evaluate the clinical utility and prognostic value of such a cut-off.

THU-325-Regional liver function investigated by galactose positron emission tomography is reduced in patients with non-alcoholic steatohepatitis

2019 ◽  
Vol 70 (1) ◽  
pp. e303
Author(s):  
Peter Lykke Eriksen ◽  
Karen Louise Thomsen ◽  
Lars Peter Larsen ◽  
Henning Gronbaek ◽  
Hendrik Vilstrup ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Liver Function ◽  
Emission Tomography ◽  
Alcoholic Steatohepatitis ◽  
Positron Emission
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