Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 18F-Fluorocholine Positron Emission Tomography-Computed Tomography: Prospective Study on Vulnerable Atheroma With Immunohistochemical Validation.

Circ Cardiovasc Imaging

From the CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands (S.V., J.C.S., F.H.B.M.S., S.H., R.J.v.O., M.E.K.); Departments of Radiology and Nuclear Medicine (S.V., R.M.K., F.H.B.M.S., R.W., M.B., F.M.M., M.E.K.), Pathology (J.C.S., S.H., J.P.M.C.), Neurology (F.H.B.M.S., R.J.v.O.), and Surgery (J.-W.H.D.), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands; Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands (M.J.A.P.D.); and Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Aachen, Germany (F.M.M.).

Published: May 2016

Background: (18)F-fluorocholine ((18)F-FCH) uptake is associated with cell proliferation and activity in tumor patients. We hypothesized that (18)F-FCH could similarly be a valuable imaging tool to identify vulnerable plaques and associated intraplaque inflammation and atheroma cell proliferation.

Methods And Results: Ten consecutive stroke patients (90% men, median age 66.5 years, range, 59.4-69.7) with ipsilateral >70% carotid artery stenosis and who underwent carotid endarterectomy were included in the study. Before carotid endarterectomy, all patients underwent positron emission tomography to assess maximum (18)F-FCH uptake in ipsilateral symptomatic carotid plaques and contralateral asymptomatic carotid arteries, which was corrected for background activity, resulting in a maximum target-to-background ratio (TBRmax). Macrophage content was assessed in all carotid endarterectomy specimens as a percentage of CD68(+)-staining per whole plaque area (plaqueCD68(+)) and as a maximum CD68(+) percentage (maxCD68(+)) in the most inflamed section/plaque. Dynamic positron emission tomography imaging demonstrated that an interval of 10 minutes between (18)F-FCH injection and positron emission tomography acquisition is appropriate for carotid plaque imaging. TBRmax in ipsilateral symptomatic carotid plaques correlated significantly with plaqueCD68(+) (Spearman's ρ=0.648, P=0.043) and maxCD68(+) (ρ=0.721, P=0.019) in the 10 corresponding carotid endarterectomy specimens. TBRmax was significantly higher (P=0.047) in ipsilateral symptomatic carotid plaques (median: 2.0; interquartile range [Q1-Q3], 1.5-2.5) compared with the contralateral asymptomatic carotid arteries (median: 1.4; Q1-Q3, 1.3-1.6). TBRmax was not significantly correlated to carotid artery stenosis (ρ=0.506, P=0.135).

Conclusions: In vivo uptake of (18)F-FCH in human carotid atherosclerotic plaques correlated strongly with degree of macrophage infiltration and recent symptoms, thus (18)F-FCH positron emission tomography is a promising tool for the evaluation of vulnerable plaques.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01899014.

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Source
http://dx.doi.org/10.1161/CIRCIMAGING.115.004467DOI Listing

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