18F-Sodium Fluoride Uptake Is a Marker of Active Calcification and Disease Progression in Patients With Aortic Stenosis

Marc R. Dweck; Will Jenkins; Alex T. Vesey; Mark A. H. Pringle; Calvin W. L. Chin; Tamir S. Malley; William J. A. Cowie; Vasiliki Tsampasian; Hamish Richardson; Alison Fletcher; William Wallace; Renzo Pessotto; Edwin J. R. van Beek; Nicholas A. Boon; James H. F. Rudd; David E. Newby

doi:10.1161/CIRCIMAGING.113.001508

18F-Sodium Fluoride Uptake Is a Marker of Active Calcification and Disease Progression in Patients With Aortic Stenosis

Marc R. Dweck^*, Will Jenkins, Alex T. Vesey, Mark A. H. Pringle, Calvin W. L. Chin, Tamir S. Malley, William J. A. Cowie, Vasiliki Tsampasian, Hamish Richardson, Alison Fletcher, William Wallace, Renzo Pessotto, Edwin J. R. van Beek, Nicholas A. Boon, James H. F. Rudd, David E. Newby

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background-

18F-Sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) are promising novel biomarkers of disease activity in aortic stenosis. We compared 18F-NaF and 18F-FDG uptake with histological characterization of the aortic valve and assessed whether they predicted disease progression.

Methods and Results-

Thirty patients with aortic stenosis underwent combined positron emission and computed tomography using 18F-NaF and 18F-FDG radiotracers. In 12 patients undergoing aortic valve replacement surgery (10 for each tracer), radiotracer uptake (mean tissue/background ratio) was compared with CD68 (inflammation), alkaline phosphatase, and osteocalcin (calcification) immunohistochemistry of the excised valve. In 18 patients (6 aortic sclerosis, 5 mild, and 7 moderate), aortic valve computed tomography calcium scoring was performed at baseline and after 1 year. Aortic valve 18F-NaF uptake correlated with both alkaline phosphatase (r=0.65; P=0.04) and osteocalcin (r=0.68; P=0.03) immunohistochemistry. There was no significant correlation between 18F-FDG uptake and CD68 staining (r=-0.43; P=0.22). After 1 year, aortic valve calcification increased from 314 (193-540) to 365 (207-934) AU (P <0.01). Baseline 18F-NaF uptake correlated closely with the change in calcium score (r=0.66; P <0.01), and this improved further (r=0.75; P <0.01) when 18F-NaF uptake overlying computed tomography-defined macrocalcification was excluded. No significant correlation was noted between valvular 18F-FDG uptake and change in calcium score (r=-0.11; P=0.66).

Conclusions-

18F-NaF uptake identifies active tissue calcification and predicts disease progression in patients with calcific aortic stenosis.

Clinical Trial Registration-

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.

Original language	English
Pages (from-to)	371-378
Number of pages	8
Journal	Circulation: Cardiovascular Imaging
Volume	7
Issue number	2
DOIs	https://doi.org/10.1161/CIRCIMAGING.113.001508
Publication status	Published - Mar 2014

Keywords / Materials (for Non-textual outputs)

fluorodeoxyglucose F18
calcification, physiologic
aortic valve stenosis
inflammation
positron-emission tomography
POSITRON-EMISSION-TOMOGRAPHY
ATHEROSCLEROTIC PLAQUE
VALVE CALCIFICATION
INFLAMMATION
PET/CT

Access to Document

10.1161/CIRCIMAGING.113.001508

Fellowship for W Jenkins: Identification of In Vivo Angiogenesis and Fibrosis in Cardiovascular Disease using Positron Emission Tomography
Newby, D. (Principal Investigator)
UK-based charities
1/11/12 → 31/10/15
Project: Research
Role of 18F-Fluoride imaging as a novel marker of plaque instability
Newby, D. (Principal Investigator)
UK-based charities
1/08/12 → 31/07/14
Project: Research
BHF Scholarship scheme - Dr Dweck
Newby, D. (Principal Investigator)
UK-based charities
1/12/09 → 28/02/11
Project: Research

Cite this

Dweck, M. R., Jenkins, W., Vesey, A. T., Pringle, M. A. H., Chin, C. W. L., Malley, T. S., Cowie, W. J. A., Tsampasian, V., Richardson, H., Fletcher, A., Wallace, W., Pessotto, R., van Beek, E. J. R., Boon, N. A., Rudd, J. H. F., & Newby, D. E. (2014). 18F-Sodium Fluoride Uptake Is a Marker of Active Calcification and Disease Progression in Patients With Aortic Stenosis. Circulation: Cardiovascular Imaging, 7(2), 371-378. https://doi.org/10.1161/CIRCIMAGING.113.001508

@article{3678d7611be340eb8ebc2749a8bb3698,

title = "18F-Sodium Fluoride Uptake Is a Marker of Active Calcification and Disease Progression in Patients With Aortic Stenosis",

abstract = "Background-18F-Sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) are promising novel biomarkers of disease activity in aortic stenosis. We compared 18F-NaF and 18F-FDG uptake with histological characterization of the aortic valve and assessed whether they predicted disease progression.Methods and Results-Thirty patients with aortic stenosis underwent combined positron emission and computed tomography using 18F-NaF and 18F-FDG radiotracers. In 12 patients undergoing aortic valve replacement surgery (10 for each tracer), radiotracer uptake (mean tissue/background ratio) was compared with CD68 (inflammation), alkaline phosphatase, and osteocalcin (calcification) immunohistochemistry of the excised valve. In 18 patients (6 aortic sclerosis, 5 mild, and 7 moderate), aortic valve computed tomography calcium scoring was performed at baseline and after 1 year. Aortic valve 18F-NaF uptake correlated with both alkaline phosphatase (r=0.65; P=0.04) and osteocalcin (r=0.68; P=0.03) immunohistochemistry. There was no significant correlation between 18F-FDG uptake and CD68 staining (r=-0.43; P=0.22). After 1 year, aortic valve calcification increased from 314 (193-540) to 365 (207-934) AU (P <0.01). Baseline 18F-NaF uptake correlated closely with the change in calcium score (r=0.66; P <0.01), and this improved further (r=0.75; P <0.01) when 18F-NaF uptake overlying computed tomography-defined macrocalcification was excluded. No significant correlation was noted between valvular 18F-FDG uptake and change in calcium score (r=-0.11; P=0.66).Conclusions-18F-NaF uptake identifies active tissue calcification and predicts disease progression in patients with calcific aortic stenosis.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.",

keywords = "fluorodeoxyglucose F18, calcification, physiologic, aortic valve stenosis, inflammation, positron-emission tomography, POSITRON-EMISSION-TOMOGRAPHY, ATHEROSCLEROTIC PLAQUE, VALVE CALCIFICATION, INFLAMMATION, PET/CT",

author = "Dweck, {Marc R.} and Will Jenkins and Vesey, {Alex T.} and Pringle, {Mark A. H.} and Chin, {Calvin W. L.} and Malley, {Tamir S.} and Cowie, {William J. A.} and Vasiliki Tsampasian and Hamish Richardson and Alison Fletcher and William Wallace and Renzo Pessotto and {van Beek}, {Edwin J. R.} and Boon, {Nicholas A.} and Rudd, {James H. F.} and Newby, {David E.}",

year = "2014",

month = mar,

doi = "10.1161/CIRCIMAGING.113.001508",

language = "English",

volume = "7",

pages = "371--378",

journal = "Circulation: Cardiovascular Imaging",

issn = "1941-9651",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "2",

}

Dweck, MR, Jenkins, W, Vesey, AT, Pringle, MAH, Chin, CWL, Malley, TS, Cowie, WJA, Tsampasian, V, Richardson, H, Fletcher, A, Wallace, W, Pessotto, R, van Beek, EJR, Boon, NA, Rudd, JHF & Newby, DE 2014, '18F-Sodium Fluoride Uptake Is a Marker of Active Calcification and Disease Progression in Patients With Aortic Stenosis', Circulation: Cardiovascular Imaging, vol. 7, no. 2, pp. 371-378. https://doi.org/10.1161/CIRCIMAGING.113.001508

TY - JOUR

T1 - 18F-Sodium Fluoride Uptake Is a Marker of Active Calcification and Disease Progression in Patients With Aortic Stenosis

AU - Dweck, Marc R.

AU - Jenkins, Will

AU - Vesey, Alex T.

AU - Pringle, Mark A. H.

AU - Chin, Calvin W. L.

AU - Malley, Tamir S.

AU - Cowie, William J. A.

AU - Tsampasian, Vasiliki

AU - Richardson, Hamish

AU - Fletcher, Alison

AU - Wallace, William

AU - Pessotto, Renzo

AU - van Beek, Edwin J. R.

AU - Boon, Nicholas A.

AU - Rudd, James H. F.

AU - Newby, David E.

PY - 2014/3

Y1 - 2014/3

N2 - Background-18F-Sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) are promising novel biomarkers of disease activity in aortic stenosis. We compared 18F-NaF and 18F-FDG uptake with histological characterization of the aortic valve and assessed whether they predicted disease progression.Methods and Results-Thirty patients with aortic stenosis underwent combined positron emission and computed tomography using 18F-NaF and 18F-FDG radiotracers. In 12 patients undergoing aortic valve replacement surgery (10 for each tracer), radiotracer uptake (mean tissue/background ratio) was compared with CD68 (inflammation), alkaline phosphatase, and osteocalcin (calcification) immunohistochemistry of the excised valve. In 18 patients (6 aortic sclerosis, 5 mild, and 7 moderate), aortic valve computed tomography calcium scoring was performed at baseline and after 1 year. Aortic valve 18F-NaF uptake correlated with both alkaline phosphatase (r=0.65; P=0.04) and osteocalcin (r=0.68; P=0.03) immunohistochemistry. There was no significant correlation between 18F-FDG uptake and CD68 staining (r=-0.43; P=0.22). After 1 year, aortic valve calcification increased from 314 (193-540) to 365 (207-934) AU (P <0.01). Baseline 18F-NaF uptake correlated closely with the change in calcium score (r=0.66; P <0.01), and this improved further (r=0.75; P <0.01) when 18F-NaF uptake overlying computed tomography-defined macrocalcification was excluded. No significant correlation was noted between valvular 18F-FDG uptake and change in calcium score (r=-0.11; P=0.66).Conclusions-18F-NaF uptake identifies active tissue calcification and predicts disease progression in patients with calcific aortic stenosis.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.

AB - Background-18F-Sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) are promising novel biomarkers of disease activity in aortic stenosis. We compared 18F-NaF and 18F-FDG uptake with histological characterization of the aortic valve and assessed whether they predicted disease progression.Methods and Results-Thirty patients with aortic stenosis underwent combined positron emission and computed tomography using 18F-NaF and 18F-FDG radiotracers. In 12 patients undergoing aortic valve replacement surgery (10 for each tracer), radiotracer uptake (mean tissue/background ratio) was compared with CD68 (inflammation), alkaline phosphatase, and osteocalcin (calcification) immunohistochemistry of the excised valve. In 18 patients (6 aortic sclerosis, 5 mild, and 7 moderate), aortic valve computed tomography calcium scoring was performed at baseline and after 1 year. Aortic valve 18F-NaF uptake correlated with both alkaline phosphatase (r=0.65; P=0.04) and osteocalcin (r=0.68; P=0.03) immunohistochemistry. There was no significant correlation between 18F-FDG uptake and CD68 staining (r=-0.43; P=0.22). After 1 year, aortic valve calcification increased from 314 (193-540) to 365 (207-934) AU (P <0.01). Baseline 18F-NaF uptake correlated closely with the change in calcium score (r=0.66; P <0.01), and this improved further (r=0.75; P <0.01) when 18F-NaF uptake overlying computed tomography-defined macrocalcification was excluded. No significant correlation was noted between valvular 18F-FDG uptake and change in calcium score (r=-0.11; P=0.66).Conclusions-18F-NaF uptake identifies active tissue calcification and predicts disease progression in patients with calcific aortic stenosis.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.

KW - fluorodeoxyglucose F18

KW - calcification, physiologic

KW - aortic valve stenosis

KW - inflammation

KW - positron-emission tomography

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - ATHEROSCLEROTIC PLAQUE

KW - VALVE CALCIFICATION

KW - INFLAMMATION

KW - PET/CT

U2 - 10.1161/CIRCIMAGING.113.001508

DO - 10.1161/CIRCIMAGING.113.001508

M3 - Article

C2 - 24508669

SN - 1941-9651

VL - 7

SP - 371

EP - 378

JO - Circulation: Cardiovascular Imaging

JF - Circulation: Cardiovascular Imaging

IS - 2

ER -

18F-Sodium Fluoride Uptake Is a Marker of Active Calcification and Disease Progression in Patients With Aortic Stenosis

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

Fellowship for W Jenkins: Identification of In Vivo Angiogenesis and Fibrosis in Cardiovascular Disease using Positron Emission Tomography

Role of 18F-Fluoride imaging as a novel marker of plaque instability

BHF Scholarship scheme - Dr Dweck

Cite this