Journal
ACS NANO
Volume 12, Issue 9, Pages 9300-9308Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b04158
Keywords
atherosclerosis; vulnerable plaque; H-ferritin; SPECT imaging; PET imaging
Categories
Funding
- National Key R&D Program of China [2017YFA0205501]
- National Natural Science Foundation of China [81722024, 81571728, 81471706, 81671735]
- Key Research of Frontier Sciences [QYZDY-SSW-SMC013]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDA09030306, XDPB0304]
- Shanghai Science and Technology Committee International Collaboration Project [16410722700]
- Youth Innovation Promotion Association of Chinese Academy of Sciences [2014078]
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Inflammation and calcification concomitantly drive atherosclerotic plaque progression and rupture and are the compelling targets for identifying plaque vulnerability. However, current imaging modalities for vulnerable atherosclerotic plaques are often limited by inadequate specificity and sensitivity. Here, we show that natural H-ferritin nanocages radiolabeled with technetium99m (Tc-99m-HFn) can identify and accurately localize macrophage-rich, atherosclerotic plaques in living mice using combined SPECT and CT. Focal Tc-99m-HFn uptake was observed in the atherosclerotic plaques with multiple high-risk features of macrophage infiltration, active calcification, positive remodeling, and necrosis on histology and in early active ongoing lesions with intense macrophage infiltration. The uptake of Tc-99m-HEn in plaques enabled quantitative measuring of the dynamic changes of inflammation during plaque progression and anti-inflammation treatment. This strategy lays the foundation of using bioengineered endogenous human ferritin nanocages for the identification of vulnerable and early active plaques as well as potential assessment of anti-inflammation therapy.
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