Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging.
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.


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.


CONCLUSIONS
These results could justify and facilitate clinical trials to evaluate the use of protease-sensing molecular optical imaging in human atherosclerosis patients.
Kim
Dong-Eog
DE
Department of Neurology, Dongguk University Ilsan Hospital, 814 Siksa-dong, Goyang, Korea. kdongeog@duih.org
Kim
Jeong-Yeon
JY
Schellingerhout
Dawid
D
Kim
Eo-Jin
EJ
Kim
Hyang Kyoung
HK
Lee
Seulki
S
Kim
Kwangmeyung
K
Kwon
Ick Chan
IC
Shon
Soo-Min
SM
Jeong
Sang-Wuk
SW
Im
So-Hyang
SH
Lee
Dong Kun
DK
Lee
Myoung Mook
MM
Kim
Geun-Eun
GE
D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D016893:Carotid Stenosis / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D002401:Cathepsin B; D016894:Endarterectomy, Carotid; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D057054:Molecular Imaging / Q000379:methods*; D010447:Peptide Hydrolases; D011446:Prospective Studies; D012189:Retrospective Studies; D015607:Stents; D014463:Ultrasonography
D005456:Fluorescent Dyes; D010447:Peptide Hydrolases; D002401:Cathepsin B; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9