Author/Authors :
Hellberg, Sanna University of Turku - Kiinamyllynkatu - Turku, Finland , Liljenback, Heidi University of Turku - Kiinamyllynkatu - Turku, Finland , Eskola, Olli University of Turku - Kiinamyllynkatu - Turku, Finland , Morisson-Iveson, Veronique White Lion Road - Amersham - Buckinghamshire, UK , Morrison, Matthew White Lion Road - Amersham - Buckinghamshire, UK , Trigg, William White Lion Road - Amersham - Buckinghamshire, UK , Saukko, Pekka Department of Pathology and Forensic Medicine - University of Turku - Kiinamyllynkatu - Turku, Finland , Yla-Herttuala, Seppo Kuopio University Hospital - Puijonlaaksontie - Kuopio, Finland , Knuuti, Juhani University of Turku - Kiinamyllynkatu - Turku, Finland , Saraste, Antti University of Turku - Kiinamyllynkatu - Turku, Finland , Roivainen, Anne University of Turku - Kiinamyllynkatu - Turku, Finland
Abstract :
Intraplaque inflammation plays an important role in the progression of atherosclerosis. The 18 kDa translocator protein (TSPO)
expression is upregulated in activated macrophages, representing a potential target to identify inflamed atherosclerotic plaques. We
preclinically evaluated 18F-GE-180, a novel third-generation TSPO radioligand, in a mouse model of atherosclerosis. Methods. Nine
hypercholesterolemic mice de cient in low density lipoprotein receptor and apolipoprotein B48 (LDLR−/−
ApoB100/100) and six healthy
C57BL/6N mice were injected with 10 MBq of 18F-GE-180. Specicity of binding was demonstrated in three LDLR−/−
ApoB100/100 mice
by injection of nonradioactive reference compound of 18F-GE-180 before 18F-GE-180. Dynamic 30-minute PET was performed
followed by contrast-enhanced CT, and the mice were sacriced at 60 minutes after injection. Tissue samples were obtained for ex vivo
biodistribution measurements, and aortas were cut into serial cryosections for digital autoradiography. The presence of macrophages
and TSPO was studied by immunohistochemistry. The 18F-GE-180 retention in plaque areas with different macrophage densities and
lesion-free vessel wall were compared. Results. The LDLR−/−
ApoB100/100 mice showed large, inflamed plaques in the aorta. Autoradiography revealed signicantly higher 18F-GE-180 retention in macrophage-rich plaque areas than in noninfiamed areas (count
densities 150 ± 45 PSL/mm2 versus 51 ±12 PSL/mm2
, p < 0.001). Prominent retention in the vessel wall without plaque was also
observed (220 ±41 PSL/mm2
). Blocking with nonradioactive GE-180 diminished the difference in count densities between
macrophage-rich and noninflamed areas in atherosclerotic plaques and lowered the count density in vessel wall without plaque.
Conclusion. 18F-GE-180 shows specic uptake in macrophage-rich areas of atherosclerotic plaques in mice. However, retention in
atherosclerotic lesions does not exceed that in lesion-free vessel wall. The third-generation TSPO radioligand 18F-GE-180 did not show
improved characteristics for imaging atherosclerotic plaque inflammation compared to previously studied TSPO-targeting tracers.
Keywords :
18F-GE , Macrophages , Tomography , PET/CT