Abstract 18873: Al18F-NOTA-folate Accumulates in Atherosclerotic Plaques and Can be Detected by PET/CT
Introduction:Macrophages are a major cell type in inflamed atherosclerotic plaques. Since folate receptor β (FR-β) is highly expressed in activated macrophages, we hypothesized that it might serve as a new marker for inflamed atherosclerotic plaques.
Hypothesis: We aimed at evaluating a FR-β targeted PET tracer, Al18F NOTA-Folate, for the detection of inflamed atherosclerotic plaques.
Methods:Atherosclerotic mice deficient for low density lipoprotein receptor (LDLR-/-ApoB100/100, n=12), C57BL control mice (n=9), and Watanabe rabbits (n=4) with endothelial denudation-induced atherosclerosis in the aorta were used. Biodistribution of Al18F-NOTA-Folate (specific radioactivity 130 GMq/μmol) was investigated in vivo by PET/contrast enhanced CT and ex vivo by gamma counting and autoradiography of aortic sections. In addition, prior to Al18F-NOTA-Folate study, the Watanabe rabbits were PET/CT imaged with 18F-FDG.
Results:Atherosclerotic mice demonstrated large and macrophage-rich atheromatous plaques in the aorta. The in vivo PET/CT revealed significantly higher uptake of Al18F-NOTA-Folate in the aortic arch of atherosclerotic mice compared to controls (aorta-to-blood ratio 1.5±0.3 vs. 0.7±0.2, P<0.0001), which were verified by ex vivo measurements. Autoradiography confirmed focally increased uptake of Al18F-NOTA-Folate in the atherosclerotic plaques (plaque-to-normal vessel wall ratio 2.6±0.7, P<0.0001). Competitive study with excess of unlabelled folate reduced Al18F-NOTA-Folate uptake in the aorta by app. 80% and thus verified the specificity of its binding. In the rabbit aorta, the PET/CT showed a strong focal in vivo uptake of Al18F-NOTA-Folate co-localizing with an atherosclerotic abdominal aorta with highest aorta-to-blood ratio of 6.0. For comparison, with 18F-FDG the ratio was 2.4 in the same area.
Conclusions: Al18F-NOTA-Folate, targeting FR-β, accumulates in macrophage-rich atherosclerotic plaques, which can be detected in vivo by PET/CT in experimental models of atherosclerosis. Further development of the tracer for imaging of patients with atherosclerosis is warranted.
Author Disclosures: J.M. Silvola: None. X. Li: None. J. Virta: None. G. Prasad Padmasola: None. P. Marjamäki: None. H. Liljenbäck: None. M. Tarkia: None. J. Hytönen: None. V. Saunavaara: None. S. Ylä-Herttuala: None. Q. Chen: None. P.S. Low: Employment; Significant; Endocyte. Research Grant; Significant; Endocyte. Ownership Interest; Significant; Endocyte. Consultant/Advisory Board; Significant; Endocyte. J. Knuuti: None. A. Saraste: None. A. Roivainen: None.
- © 2015 by American Heart Association, Inc.