Evaluation of alphavbeta3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice.
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.
Laitinen
Iina
I
Nuklearmedizinische Klinik der TU Muenchen, Technische Universitaet Muenchen, Munich, Germany.
Saraste
Antti
A
Weidl
Eliane
E
Poethko
Thorsten
T
Weber
Axel W
AW
Nekolla
Stephan G
SG
Leppänen
Pia
P
Ylä-Herttuala
Seppo
S
Hölzlwimmer
Gabriele
G
Walch
Axel
A
Esposito
Irene
I
Wester
Hans-Jürgen
HJ
Knuuti
Juhani
J
Schwaiger
Markus
M
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
D053299:Apolipoprotein B-100; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D011973:Receptors, LDL; C423503:fluorogalacto-RGD; D014316:Tritium; D003847:Deoxyglucose; D005690:Galactose