18Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis

Rozh H. Al-Mashhadi; Lars P. Tolbod; Lars Bloch; Martin M. Bjørklund; Zahra P. Nasr; Zheer Al-Mashhadi; Michael Winterdahl; Jørgen Frøkiær; Erling Falk; Jacob F. Bentzon

doi:10.1016/j.jacc.2019.06.057

¹⁸Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis

Rozh H. Al-Mashhadi^*, Lars P. Tolbod, Lars Bloch, Martin M. Bjørklund, Zahra P. Nasr, Zheer Al-Mashhadi, Michael Winterdahl, Jørgen Frøkiær, Erling Falk, Jacob F. Bentzon

^*Corresponding author for this work

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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.

Original language	English
Journal	Journal of the American College of Cardiology
Volume	74
Issue	9
Pages (from-to)	1220-1232
Number of pages	13
ISSN	0735-1097
DOIs	https://doi.org/10.1016/j.jacc.2019.06.057
Publication status	Published - 2019

Keywords

ATHEROSCLEROTIC PLAQUE INFLAMMATION
FDG-PET
HYPOXIA
INHIBITOR
MACROPHAGES
PET/CT
WALL INFLAMMATION
atherosclerosis
fluorodeoxyglucose
macrophages
signal model

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1-s2.0-S0735109719358279-mainFinal published version, 3.24 MBLicence: CC BY-NC-ND

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@article{ddfae2c6d7044ff0aba9dfa962812471,

title = "18Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis",

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.",

keywords = "ATHEROSCLEROTIC PLAQUE INFLAMMATION, FDG-PET, HYPOXIA, INHIBITOR, MACROPHAGES, PET/CT, WALL INFLAMMATION, atherosclerosis, fluorodeoxyglucose, macrophages, signal model",

author = "Al-Mashhadi, {Rozh H.} and Tolbod, {Lars P.} and Lars Bloch and Bj{\o}rklund, {Martin M.} and Nasr, {Zahra P.} and Zheer Al-Mashhadi and Michael Winterdahl and J{\o}rgen Fr{\o}ki{\ae}r and Erling Falk and Bentzon, {Jacob F.}",

year = "2019",

doi = "10.1016/j.jacc.2019.06.057",

language = "English",

volume = "74",

pages = "1220--1232",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "9",

}

¹⁸Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis. / Al-Mashhadi, Rozh H.; Tolbod, Lars P.; Bloch, Lars et al.
In: Journal of the American College of Cardiology, Vol. 74, No. 9, 2019, p. 1220-1232.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - 18Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis

AU - Al-Mashhadi, Rozh H.

AU - Tolbod, Lars P.

AU - Bloch, Lars

AU - Bjørklund, Martin M.

AU - Nasr, Zahra P.

AU - Al-Mashhadi, Zheer

AU - Winterdahl, Michael

AU - Frøkiær, Jørgen

AU - Falk, Erling

AU - Bentzon, Jacob F.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - ATHEROSCLEROTIC PLAQUE INFLAMMATION

KW - FDG-PET

KW - HYPOXIA

KW - INHIBITOR

KW - MACROPHAGES

KW - PET/CT

KW - WALL INFLAMMATION

KW - atherosclerosis

KW - fluorodeoxyglucose

KW - macrophages

KW - signal model

UR - http://www.scopus.com/inward/record.url?scp=85070927737&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2019.06.057

DO - 10.1016/j.jacc.2019.06.057

M3 - Journal article

C2 - 31466620

AN - SCOPUS:85070927737

SN - 0735-1097

VL - 74

SP - 1220

EP - 1232

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 9

ER -

¹⁸Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis

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