title: Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 18F-Fluorocholine Positron Emission Tomography-Computed Tomography: Prospective Study on Vulnerable Atheroma With Immunohistochemical Validation.
abstract: (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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01899014.
authors.affiliation: 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.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Vöö
authors.affiliation: 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.).
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kwee
authors.affiliation: 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.).
authors.forename: Judith C
authors.initials: JC
authors.lastname: Sluimer
authors.affiliation: 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.).
authors.forename: Floris H B M
authors.initials: FH
authors.lastname: Schreuder
authors.affiliation: 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.).
authors.forename: Roel
authors.initials: R
authors.lastname: Wierts
authors.affiliation: 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.).
authors.forename: Matthias
authors.initials: M
authors.lastname: Bauwens
authors.affiliation: 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.).
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.affiliation: 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.).
authors.forename: Jack P M
authors.initials: JP
authors.lastname: Cleutjens
authors.affiliation: 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.).
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Oostenbrugge
authors.affiliation: 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.).
authors.forename: Jan-Willem H
authors.initials: JW
authors.lastname: Daemen
authors.affiliation: 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.).
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.affiliation: 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.). eline.kooi@mumc.nl fmottaghy@ukaachen.de.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: 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.). eline.kooi@mumc.nl fmottaghy@ukaachen.de.
authors.forename: M Eline
authors.initials: ME
authors.lastname: Kooi
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D016893:Carotid Stenosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003430:Cross-Sectional Studies; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008264:Macrophages / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic; D000072078:Positron Emission Tomography Computed Tomography; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D012422:Rupture, Spontaneous; D012720:Severity of Illness Index; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D002794:Choline; D019275:Radiopharmaceuticals; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C514960:fluorocholine
keywords: atherosclerosis; carotid artery diseases; endarterectomy; fluorocholine; inflammation; macrophages; positron-emission tomography