Protease Imaging of Human Atheromata Captures Molecular Information of Atherosclerosis, Complementing Anatomic Imaging
- Protease Imaging of Human Atheromata Captures Molecular Information of Atherosclerosis, Complementing Anatomic Imaging
- 김동억; 김정연; DawidSchellingerhout; 김어진; 김향경; 이슬기; 김광명; 권익찬; 손수민; 정상욱; 임소향; 이동건; 이명묵; 김근은
- atherosclerosis; cathepsin-B; molecular imaging; protease; structural imaging
- Issue Date
- Arteriosclerosis, thrombosis, and vascular biology
- VOL 30, NO 3, 449-456
- Objective—There is hope that molecular imaging can identify vulnerable atherosclerotic plaques. However, there is a
paucity of clinical translational data to guide the future development of this field. Here, we cross-correlate cathepsin-B
or matrix metalloproteinase-2/-9 molecular optical imaging data of human atheromata or emboli with conventional
imaging data, clinical data, and histopathologic data.
Methods and Results—Fifty-two patients undergoing carotid endarterectomy (41 atheromata) or carotid stenting (15
captured emboli) were studied with protease-activatable imaging probes. We show that protease-related fluorescent
signal in carotid atheromata or in emboli closely reflects the pathophysiologic alterations of plaque inflammation and
statin-mediated therapeutic effects on plaque inflammation. Inflammation-related fluorescent signal was observed in the
carotid bifurcation area and around ulcero-hemorrhagic lesions. Pathologically proven unstable plaques had high
cathepsin-B–related fluorescent signal. The distribution patterns of the mean cathepsin-B imaging signals showed a
difference between the symptomatic vs asymptomatic plaque groups. However, the degree of carotid stenosis or
ultrasonographic echodensity was weakly correlated with the inflammatory proteolytic enzyme-related signal,
suggesting that molecular imaging yields complimentary new information not available to conventional imaging.
Conclusion—These results could justify and facilitate clinical trials to evaluate the use of protease-sensing molecular
optical imaging in human atherosclerosis patients.
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