18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.
BACKGROUND
The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG).


METHODS
In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction.


RESULTS
In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001).


CONCLUSIONS
(18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease.


BACKGROUND
Chief Scientist Office Scotland and British Heart Foundation.
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK. Electronic address: nikhil.joshi@ed.ac.uk.
Nikhil V
NV
Joshi
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Alex T
AT
Vesey
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Michelle C
MC
Williams
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Anoop S V
AS
Shah
Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
Patrick A
PA
Calvert
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Felicity H M
FH
Craighead
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Su Ern
SE
Yeoh
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
William
W
Wallace
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Donald
D
Salter
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Alison M
AM
Fletcher
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Edwin J R
EJ
van Beek
Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, UK.
Andrew D
AD
Flapan
Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, UK.
Neal G
NG
Uren
Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, UK.
Miles W H
MW
Behan
Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, UK.
Nicholas L M
NL
Cruden
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Nicholas L
NL
Mills
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Keith A A
KA
Fox
Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
James H F
JH
Rudd
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
Marc R
MR
Dweck
Centre for Cardiovascular Science, Clinical Research Imaging Centre, and Division of Pathology, University of Edinburgh, Edinburgh, UK.
David E
DE
Newby
D000368:Aged; D000787:Angina Pectoris / Q000378:metabolism; D016893:Carotid Stenosis / Q000175:diagnosis / Q000378:metabolism; D015986:Confounding Factors, Epidemiologic; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000175:diagnosis / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000378:metabolism*; D012307:Risk Factors; D012422:Rupture, Spontaneous; D012606:Scotland; D012969:Sodium Fluoride / Q000378:metabolism; D014057:Tomography, X-Ray Computed
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D012969:Sodium Fluoride