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. 2016 May;9(5):e004467. doi: 10.1161/CIRCIMAGING.115.004467.

Abstract

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.

Keywords: atherosclerosis; carotid artery diseases; endarterectomy; fluorocholine; inflammation; macrophages; positron-emission tomography.

MeSH terms

  • Aged
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Asymptomatic Diseases
  • Biomarkers / analysis
  • Carotid Arteries / chemistry
  • Carotid Arteries / diagnostic imaging*
  • Carotid Arteries / pathology
  • Carotid Arteries / surgery
  • Carotid Stenosis / diagnostic imaging*
  • Carotid Stenosis / metabolism
  • Carotid Stenosis / pathology
  • Carotid Stenosis / surgery
  • Choline / administration & dosage
  • Choline / analogs & derivatives*
  • Cross-Sectional Studies
  • Endarterectomy, Carotid
  • Female
  • Humans
  • Immunohistochemistry*
  • Inflammation / diagnostic imaging*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / surgery
  • Macrophages / chemistry
  • Macrophages / pathology*
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic*
  • Positron Emission Tomography Computed Tomography*
  • Predictive Value of Tests
  • Prospective Studies
  • Radiopharmaceuticals / administration & dosage*
  • Rupture, Spontaneous
  • Severity of Illness Index

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD68 antigen, human
  • Radiopharmaceuticals
  • fluorocholine
  • Choline

Associated data

  • ClinicalTrials.gov/NCT01899014