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18F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression

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Ludvigsen, Trine P ; Pedersen, Sune F ; Vegge, Andreas ; Ripa, Rasmus S ; Johannesen, Helle H ; Hansen, Adam E ; Löfgren, Johan ; Schumacher-Petersen, Camilla ; Kirk, Rikke K ; Pedersen, Henrik D ; Christoffersen, Berit Ø ; Ørbæk, Mathilde ; Forman, Julie L ; Klausen, Thomas L ; Olsen, Lisbeth H ; Kjaer, Andreas. / 18F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis : Correlations with histology and quantitative gene expression. I: Atherosclerosis. 2019 ; Bind 285. s. 55-63.

Bibtex

@article{58ef075f5b904aa5b782b591aebec1c3,
title = "18F-FDG PET/MR-imaging in a G{\"o}ttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression",
abstract = "BACKGROUND AND AIMS: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using 18F-fluorodeoxyglucose (18F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis.METHODS: G{\"o}ttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, 18F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression.RESULTS: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBRMax (95% confidence interval) CITBRMax: 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CITBRMax: -5.94;-0.07). No difference was observed between DNO and Control (CITBRMax: -2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρs = 0.58; MMP9, ρs = 0.46; SPP1, ρs = 0.44 and CTSK, ρs = 0.49; (p ≤ 0.01 for all).CONCLUSIONS: In a model of atherosclerosis, 18F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation.",
author = "Ludvigsen, {Trine P} and Pedersen, {Sune F} and Andreas Vegge and Ripa, {Rasmus S} and Johannesen, {Helle H} and Hansen, {Adam E} and Johan L{\"o}fgren and Camilla Schumacher-Petersen and Kirk, {Rikke K} and Pedersen, {Henrik D} and Christoffersen, {Berit {\O}} and Mathilde {\O}rb{\ae}k and Forman, {Julie L} and Klausen, {Thomas L} and Olsen, {Lisbeth H} and Andreas Kjaer",
note = "Copyright {\textcopyright} 2019. Published by Elsevier B.V.",
year = "2019",
month = jun,
doi = "10.1016/j.atherosclerosis.2019.04.209",
language = "English",
volume = "285",
pages = "55--63",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - 18F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis

T2 - Correlations with histology and quantitative gene expression

AU - Ludvigsen, Trine P

AU - Pedersen, Sune F

AU - Vegge, Andreas

AU - Ripa, Rasmus S

AU - Johannesen, Helle H

AU - Hansen, Adam E

AU - Löfgren, Johan

AU - Schumacher-Petersen, Camilla

AU - Kirk, Rikke K

AU - Pedersen, Henrik D

AU - Christoffersen, Berit Ø

AU - Ørbæk, Mathilde

AU - Forman, Julie L

AU - Klausen, Thomas L

AU - Olsen, Lisbeth H

AU - Kjaer, Andreas

N1 - Copyright © 2019. Published by Elsevier B.V.

PY - 2019/6

Y1 - 2019/6

N2 - BACKGROUND AND AIMS: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using 18F-fluorodeoxyglucose (18F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis.METHODS: Göttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, 18F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression.RESULTS: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBRMax (95% confidence interval) CITBRMax: 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CITBRMax: -5.94;-0.07). No difference was observed between DNO and Control (CITBRMax: -2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρs = 0.58; MMP9, ρs = 0.46; SPP1, ρs = 0.44 and CTSK, ρs = 0.49; (p ≤ 0.01 for all).CONCLUSIONS: In a model of atherosclerosis, 18F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation.

AB - BACKGROUND AND AIMS: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using 18F-fluorodeoxyglucose (18F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis.METHODS: Göttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups, 18F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression.RESULTS: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBRMax (95% confidence interval) CITBRMax: 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CITBRMax: -5.94;-0.07). No difference was observed between DNO and Control (CITBRMax: -2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρs = 0.58; MMP9, ρs = 0.46; SPP1, ρs = 0.44 and CTSK, ρs = 0.49; (p ≤ 0.01 for all).CONCLUSIONS: In a model of atherosclerosis, 18F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation.

U2 - 10.1016/j.atherosclerosis.2019.04.209

DO - 10.1016/j.atherosclerosis.2019.04.209

M3 - Journal article

C2 - 31004968

VL - 285

SP - 55

EP - 63

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

ER -

ID: 59157529