RT Journal Article
SR Electronic
T1 Multimodality and Molecular Imaging of Matrix Metalloproteinase Activation in Calcific Aortic Valve Disease
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 933
OP 938
DO 10.2967/jnumed.114.152355
VO 56
IS 6
A1 Jung, Jae-Joon
A1 Razavian, Mahmoud
A1 Challa, Azariyas A.
A1 Nie, Lei
A1 Golestani, Reza
A1 Zhang, Jiasheng
A1 Ye, Yunpeng
A1 Russell, Kerry S.
A1 Robinson, Simon P.
A1 Heistad, Donald D.
A1 Sadeghi, Mehran M.
YR 2015
UL http://jnm.snmjournals.org/content/56/6/933.abstract
AB Calcific aortic valve disease (CAVD) is the most common cause of aortic stenosis. Matrix metalloproteinases (MMPs) are upregulated in CAVD and contribute to valvular remodeling and calcification. We investigated the feasibility and correlates of MMP-targeted molecular imaging for detection of valvular biology in CAVD. Methods: Apolipoprotein E–deficient (apoE−/−) mice were fed a Western diet (WD) for 3, 6, and 9 mo (n = 108) to induce CAVD. Wild-type mice served as the control group (n = 24). The development of CAVD was tracked with CT, echocardiography, MMP-targeted small-animal SPECT imaging using 99mTc-RP805, and histologic analysis. Results: Key features of CAVD—leaflet thickening and valvular calcification—were noted after 6 mo of WD and were more pronounced after 9 mo. These findings were associated with a significant reduction in aortic valve leaflet separation and a significant increase in transaortic valve flow velocity. On in vivo SPECT/CT images, MMP signal in the aortic valve area was significantly higher at 6 mo in WD mice than in control mice and decreased thereafter. The specificity of the signal was demonstrated by blocking, using an excess of nonlabeled precursor. Similar to MMP signal, MMP activity as determined by in situ zymography and valvular inflammation by CD68 staining were maximal at 6 mo. In vivo 99mTc-RP805 uptake correlated significantly with MMP activity (R2 = 0.94, P < 0.05) and CD68 expression (R2 = 0.98, P < 0.01) in CAVD. Conclusion: MMP-targeted imaging detected valvular inflammation and remodeling in a murine model of CAVD. If this ability is confirmed in humans, the technique may provide a tool for tracking the effect of emerging medical therapeutic interventions and for predicting outcome in CAVD.