Rozh H Al-Mashhadi1, Lars P Tolbod2, Lars Ø Bloch3, Martin M Bjørklund4, Zahra P Nasr5, Zheer Al-Mashhadi6, Michael Winterdahl2, Jørgen Frøkiær7, Erling Falk5, Jacob F Bentzon4. 1. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Radiology, Aarhus University Hospital, Aarhus, Denmark; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: rham@clin.au.dk. 2. Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; MR Center, Aarhus University Hospital, Aarhus, Denmark. 4. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain. 5. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. 6. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 7. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark.
Abstract
BACKGROUND: Arterial 18fluorodeoxyglucose (FDG) positron emission tomography (PET) is considered a measure of atherosclerotic plaque macrophages and is used for quantification of disease activity in clinical trials, but the distribution profile of FDG across macrophages and other arterial cells has not been fully clarified. OBJECTIVES: The purpose of this study was to analyze FDG uptake in different arterial tissues and their contribution to PET signal in normal and atherosclerotic arteries. METHODS: Wild-type and D374Y-PCSK9 transgenic Yucatan minipigs were fed a high-fat, high-cholesterol diet to induce atherosclerosis and subjected to a clinical FDG-PET and computed tomography scan protocol. Volumes of arterial media, intima/lesion, macrophage-rich, and hypoxic tissues were measured in serial histological sections. Distributions of FDG in macrophages and other arterial tissues were quantified using modeling of the in vivo PET signal. In separate transgenic minipigs, the intra-arterial localization of FDG was determined directly by autoradiography. RESULTS: Arterial FDG-PET signal appearance and intensity were similar to human imaging. The modeling approach showed high accuracy in describing the FDG-PET signal and revealed comparable FDG accumulation in macrophages and other arterial tissues, including medial smooth muscle cells. These findings were verified directly by autoradiography of normal and atherosclerotic arteries. CONCLUSIONS: FDG is taken up comparably in macrophage-rich and -poor arterial tissues in minipigs. This offers a mechanistic explanation to a growing number of observations in clinical imaging studies that have been difficult to reconcile with macrophage-selective FDG uptake.
BACKGROUND: Arterial 18fluorodeoxyglucose (FDG) positron emission tomography (PET) is considered a measure of atherosclerotic plaque macrophages and is used for quantification of disease activity in clinical trials, but the distribution profile of FDG across macrophages and other arterial cells has not been fully clarified. OBJECTIVES: The purpose of this study was to analyze FDG uptake in different arterial tissues and their contribution to PET signal in normal and atherosclerotic arteries. METHODS: Wild-type and D374Y-PCSK9 transgenic Yucatan minipigs were fed a high-fat, high-cholesterol diet to induce atherosclerosis and subjected to a clinical FDG-PET and computed tomography scan protocol. Volumes of arterial media, intima/lesion, macrophage-rich, and hypoxic tissues were measured in serial histological sections. Distributions of FDG in macrophages and other arterial tissues were quantified using modeling of the in vivo PET signal. In separate transgenic minipigs, the intra-arterial localization of FDG was determined directly by autoradiography. RESULTS: Arterial FDG-PET signal appearance and intensity were similar to human imaging. The modeling approach showed high accuracy in describing the FDG-PET signal and revealed comparable FDG accumulation in macrophages and other arterial tissues, including medial smooth muscle cells. These findings were verified directly by autoradiography of normal and atherosclerotic arteries. CONCLUSIONS:FDG is taken up comparably in macrophage-rich and -poor arterial tissues in minipigs. This offers a mechanistic explanation to a growing number of observations in clinical imaging studies that have been difficult to reconcile with macrophage-selective FDG uptake.
Authors: Marc A Miller; David H Adams; Dimosthenis Pandis; Philip M Robson; Amit Pawale; Renata Pyzik; Steve L Liao; Ahmed El-Eshmawi; Percy Boateng; Jalaj Garg; Stephen Waterford; Menachem M Weiner; Srinivas R Dukkipati; Vivek Y Reddy; Zahi A Fayad; Maria G Trivieri Journal: JAMA Cardiol Date: 2020-05-27 Impact factor: 14.676
Authors: Marc A Miller; David H Adams; Dimosthenis Pandis; Philip M Robson; Amit Pawale; Renata Pyzik; Steve L Liao; Ahmed El-Eshmawi; Percy Boateng; Jalaj Garg; Stephen Waterford; Menachem M Weiner; Srinivas R Dukkipati; Vivek Y Reddy; Zahi A Fayad; Maria G Trivieri Journal: JAMA Cardiol Date: 2020-09-01 Impact factor: 14.676
Authors: Jakub Toczek; Jing Wu; Ansel T Hillmer; Jinah Han; Irina Esterlis; Kelly P Cosgrove; Chi Liu; Mehran M Sadeghi Journal: J Nucl Cardiol Date: 2020-02-10 Impact factor: 5.952
Authors: Selim Demirdelen; Philip Z Mannes; Ali Mubin Aral; Joseph Haddad; Steven A Leers; Delphine Gomez; Sina Tavakoli Journal: J Nucl Cardiol Date: 2021-01-08 Impact factor: 3.872
Authors: Rasmus S Ripa; Emilie H Zobel; Bernt J von Scholten; Jacob K Jensen; Tina Binderup; Lars J Diaz; Viktor R Curovic; Tine W Hansen; Peter Rossing; Andreas Kjaer Journal: Circ Cardiovasc Imaging Date: 2021-06-30 Impact factor: 7.792