18F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression
| Autor: | Sune Pedersen, Mathilde Ørbæk, Berit Ø Christoffersen, Andreas Vegge, Helle Hjorth Johannesen, Thomas Levin Klausen, Trine Pagh Ludvigsen, Rasmus S. Ripa, Lisbeth H. Olsen, Julie Lyng Forman, Andreas Kjaer, Adam E. Hansen, Johan Löfgren, Rikke Kaae Kirk, Henrik D. Pedersen, Camilla Schumacher-Petersen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Aorta Pathology medicine.medical_specialty Cluster of differentiation medicine.diagnostic_test business.industry Magnetic resonance imaging Inflammation Göttingen minipig 030204 cardiovascular system & hematology 3. Good health 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Positron emission tomography medicine.artery Gene expression Cathepsin K medicine medicine.symptom Cardiology and Cardiovascular Medicine business |
| Zdroj: | Atherosclerosis. 285:55-63 |
| ISSN: | 0021-9150 |
| Popis: | 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 Gottingen 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 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. |
| Databáze: | OpenAIRE |
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