title: 64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy.
abstract: OBJECTIVE
  A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used positron emission tomography (PET) and the novel PET ligand [(64)Cu] [1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid]-d-Phe1,Tyr3-octreotate ((64)Cu-DOTATATE) to specifically target macrophages via the somatostatin receptor subtype-2 in vivo.
  
  
  RESULTS
  Ten patients underwent simultaneous PET/MRI to measure (64)Cu-DOTATATE uptake in carotid artery plaques before carotid endarterectomy. (64)Cu-DOTATATE uptake was significantly higher in symptomatic plaque versus the contralateral carotid artery (P<0.001). Subsequently, a total of 62 plaque segments were assessed for gene expression of selected markers of plaque vulnerability using real-time quantitative polymerase chain reaction. These results were compared with in vivo (64)Cu-DOTATATE uptake calculated as the mean standardized uptake value. Univariate analysis of real-time quantitative polymerase chain reaction and PET showed that cluster of differentiation 163 (CD163) and CD68 gene expression correlated significantly but weakly with mean standardized uptake value in scans performed 85 minutes post injection (P<0.001 and P=0.015, respectively). Subsequent multivariate analysis showed that CD163 correlated independently with (64)Cu-DOTATATE uptake (P=0.031) whereas CD68 did not contribute significantly to the final model.
  
  
  CONCLUSIONS
  The novel PET tracer (64)Cu-DOTATATE accumulates in atherosclerotic plaques of the carotid artery. CD163 gene expression correlated independently with (64)Cu-DOTATATE uptake measured by real-time quantitative polymerase chain reaction in the final multivariate model, indicating that (64)Cu-DOTATATE PET is detecting alternatively activated macrophages. This association could potentially improve noninvasive identification and characterization of vulnerable plaques.
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. sfolkep@sund.ku.dk.
authors.forename: Sune Folke
authors.initials: SF
authors.lastname: Pedersen
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Benjamin Vikjær
authors.initials: BV
authors.lastname: Sandholt
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sune Høgild
authors.initials: SH
authors.lastname: Keller
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Adam Espe
authors.initials: AE
authors.lastname: Hansen
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas Ettrup
authors.initials: AE
authors.lastname: Clemmensen
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Sillesen
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rasmus Sejersten
authors.initials: RS
authors.lastname: Ripa
authors.affiliation: From the Department of Clinical Physiology, Nuclear Medicine and PET (S.F.P., A.E.C., L.H., R.S.R., A.K., S.H.K., A.E.H.), Cluster for Molecular Imaging (S.F.P., A.E.C., L.H., R.S.R., A.K.), Department of Vascular Surgery (B.V.S., H.S.), Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D016893:Carotid Stenosis / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D003301:Copper Radioisotopes; D016894:Endarterectomy, Carotid; D015870:Gene Expression; D006801:Humans; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015282:Octreotide / Q000031:analogs & derivatives*; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography / Q000379:methods*; D011956:Receptors, Cell Surface / Q000235:genetics; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003301:Copper Radioisotopes; D015282:Octreotide; D009942:Organometallic Compounds; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C575629:64Cu-DOTATATE; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: atherosclerosis; carotid; endarterectomy; magnetic resonance imaging; positron-emission tomography