title: Evaluation of alphavbeta3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice.
abstract: BACKGROUND
  (18)F-Galacto-RGD is a positron emission tomography (PET) tracer binding to alpha(v)beta(3) integrin that is expressed by macrophages and endothelial cells in atherosclerotic lesions. Therefore, we evaluated (18)F-galacto-RGD for imaging vascular inflammation by studying its uptake into atherosclerotic lesions of hypercholesterolemic mice in comparison to deoxyglucose.
  
  
  RESULTS
  Hypercholesterolemic LDLR(-/-)ApoB(100/100) mice on a Western diet and normally fed adult C57BL/6 control mice were injected with (18)F-galacto-RGD and (3)H-deoxyglucose followed by imaging with a small animal PET/CT scanner. The aorta was dissected 2 hours after tracer injection for biodistribution studies, autoradiography, and histology. Biodistribution of (18)F-galacto-RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal (18)F-galacto-RGD uptake in the atherosclerotic plaques when compared with the adjacent normal vessel wall or adventitia. Plaque-to-normal vessel wall ratios were comparable to those of deoxyglucose. Although angiogenesis was not detected, (18)F-galacto-RGD uptake was associated with macrophage density and deoxyglucose accumulation in the plaques. Binding to atherosclerotic lesions was efficiently blocked in competition experiments. In vivo imaging visualized (18)F-galacto-RGD uptake colocalizing with calcified lesions of the aortic arch as seen in CT angiography.
  
  
  CONCLUSIONS
  (18)F-Galacto-RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density. (18)F-Galacto-RGD is a potential tracer for noninvasive imaging of inflammation in atherosclerotic lesions.
authors.affiliation: Nuklearmedizinische Klinik der TU Muenchen, Technische Universitaet Muenchen, Munich, Germany.
authors.forename: Iina
authors.initials: I
authors.lastname: Laitinen
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.forename: Eliane
authors.initials: E
authors.lastname: Weidl
authors.forename: Thorsten
authors.initials: T
authors.lastname: Poethko
authors.forename: Axel W
authors.initials: AW
authors.lastname: Weber
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Nekolla
authors.forename: Pia
authors.initials: P
authors.lastname: Leppänen
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hölzlwimmer
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging* / Q000378:metabolism; D001025:Aortitis / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D001027:Aortography / Q000379:methods; D053299:Apolipoprotein B-100 / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D001345:Autoradiography; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005690:Galactose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006937:Hypercholesterolemia / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008264:Macrophages / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010456:Peptides, Cyclic / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014316:Tritium
chemical_list: D053299:Apolipoprotein B-100; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D011973:Receptors, LDL; C423503:fluorogalacto-RGD; D014316:Tritium; D003847:Deoxyglucose; D005690:Galactose