Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis
Rationale: Local plaque macrophage proliferation and monocyte production in hematopoietic organs promote progression of atherosclerosis. Therefore, non-invasive imaging of proliferation could serve as a biomarker and monitor therapeutic intervention.
Objective: To explore 18F-fluorothymidine (18F-FLT) PET-CT imaging of cell proliferation in atherosclerosis.
Methods and Results: 18F-FLT PET-CT was performed in mice, rabbits and humans with atherosclerosis. In ApoE-/- mice, increased 18F-FLT signal was observed in atherosclerotic lesions, spleen and bone marrow (SUV wild-type versus ApoE-/- 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, 18F-FLT plaque signal correlated with the duration of high cholesterol diet (r2=0.33, p<0.05). Aortic 18F-FLT uptake was reduced when cell proliferation was suppressed with 5-FU in ApoE-/- mice (p<0.05). In rabbits, inflamed atherosclerotic vasculature with the highest 18F-fluorodeoxyglucose uptake enriched 18F-FLT. In patients with atherosclerosis, 18F-FLT signal significantly increased in the inflamed carotid artery and in the aorta.
Conclusions: 18F-FLT PET imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis.
- cardiac positron emission tomography
- Received June 12, 2015.
- Revision received September 21, 2015.
- Accepted September 22, 2015.