18Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis

Autor: Michael Winterdahl, Zahra P. Nasr, Zheer Al-Mashhadi, Martin M. Bjørklund, Jacob F. Bentzon, Lars Poulsen Tolbod, Jørgen Frøkiær, Rozh H Al-Mashhadi, Erling Falk, Lars Ø Bloch
Přispěvatelé: Danish Council for Independent Research, Lundbeck Foundation, Danish Heart Foundation, Aarhus University (Dinamarca), Ministerio de Ciencia, Innovación y Universidades (España), Fundación ProCNIC
Rok vydání: 2019
Předmět:
Zdroj: Al-Mashhadi, R H, Tolbod, L P, Bloch, L, Bjørklund, M M, Nasr, Z P, Al-Mashhadi, Z, Winterdahl, M, Frøkiær, J, Falk, E & Bentzon, J F 2019, ' 18 Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis ', Journal of the American College of Cardiology, vol. 74, no. 9, pp. 1220-1232 . https://doi.org/10.1016/j.jacc.2019.06.057
Repisalud
Instituto de Salud Carlos III (ISCIII)
ISSN: 0735-1097
DOI: 10.1016/j.jacc.2019.06.057
Popis: 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. This study was supported by the Danish Council for Independent Research/Medical Sciences, Lundbeck Foundation, Danish Heart Foundation, and Aarhus University Research Foundation (AU IDEAS). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation; and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Dr. Bentzon has served as a consultant for Novo Nordisk A/S; and has within the last 5 years received an investigator-initiated preclinical research grant from Regeneron Pharmaceuticals Sí
Databáze: OpenAIRE