Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis

Circ Res. 2015 Oct 23;117(10):835-45. doi: 10.1161/CIRCRESAHA.115.307024. Epub 2015 Sep 22.


Rationale: Local plaque macrophage proliferation and monocyte production in hematopoietic organs promote progression of atherosclerosis. Therefore, noninvasive imaging of proliferation could serve as a biomarker and monitor therapeutic intervention.

Objective: To explore (18)F-FLT positron emission tomography-computed tomography imaging of cell proliferation in atherosclerosis.

Methods and results: (18)F-FLT positron emission tomography-computed tomography was performed in mice, rabbits, and humans with atherosclerosis. In apolipoprotein E knock out mice, increased (18)F-FLT signal was observed in atherosclerotic lesions, spleen, and bone marrow (standardized uptake values wild-type versus apolipoprotein E knock out mice, 0.05 ± 0.01 versus 0.17 ± 0.01, P<0.05 in aorta; 0.13 ± 0.01 versus 0.28 ± 0.02, P<0.05 in bone marrow; 0.06 ± 0.01 versus 0.22 ± 0.01, P<0.05 in spleen), corroborated by ex vivo scintillation counting and autoradiography. Flow cytometry confirmed significantly higher proliferation of macrophages in aortic lesions and hematopoietic stem and progenitor cells in the spleen and bone marrow in these mice. In addition, (18)F-FLT plaque signal correlated with the duration of high cholesterol diet (r(2)=0.33, P<0.05). Aortic (18)F-FLT uptake was reduced when cell proliferation was suppressed with fluorouracil in apolipoprotein E knock out mice (P<0.05). In rabbits, inflamed atherosclerotic vasculature with the highest (18)F-fluorodeoxyglucose uptake enriched (18)F-FLT. In patients with atherosclerosis, (18)F-FLT signal significantly increased in the inflamed carotid artery and in the aorta.

Conclusions: (18)F-FLT positron emission tomography imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis.

Keywords: 18F-fluorothymidine; atherosclerosis; imaging; inflammation; macrophage; positron emission tomography; proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / diagnostic imaging
  • Aortic Diseases / diagnosis*
  • Aortic Diseases / diagnostic imaging
  • Aortic Diseases / genetics
  • Aortic Diseases / metabolism
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Atherosclerosis / diagnosis*
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Bone Marrow / diagnostic imaging
  • Carotid Artery Diseases / diagnosis*
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / genetics
  • Carotid Artery Diseases / metabolism
  • Cell Proliferation*
  • Cholesterol, Dietary
  • Dideoxynucleosides
  • Diet, High-Fat
  • Disease Models, Animal
  • Female
  • Fluorodeoxyglucose F18
  • Hematopoietic Stem Cells* / diagnostic imaging
  • Humans
  • Macrophages* / diagnostic imaging
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multimodal Imaging
  • Plaque, Atherosclerotic
  • Positron-Emission Tomography*
  • Predictive Value of Tests
  • Rabbits
  • Radiopharmaceuticals
  • Retrospective Studies
  • Spleen / diagnostic imaging
  • Time Factors
  • Tomography, X-Ray Computed*


  • Apolipoproteins E
  • Cholesterol, Dietary
  • Dideoxynucleosides
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • alovudine