PT  - JOURNAL ARTICLE
AU  - Satoru Ohshima
AU  - Artiom Petrov
AU  - Shinichiro Fujimoto
AU  - Jun Zhou
AU  - Michael Azure
AU  - D. Scott Edwards
AU  - Toyoaki Murohara
AU  - Navneet Narula
AU  - Sotirios Tsimikas
AU  - Jagat Narula
TI  - Molecular Imaging of Matrix Metalloproteinase Expression in Atherosclerotic Plaques of Mice Deficient in Apolipoprotein E or Low-Density-Lipoprotein Receptor
AID  - 10.2967/jnumed.108.055889
DP  - 2009 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 612--617
VI  - 50
IP  - 4
4099  - http://jnm.snmjournals.org/content/50/4/612.short
4100  - http://jnm.snmjournals.org/content/50/4/612.full
SO  - J Nucl Med2009 Apr 01; 50
AB  - Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques and play an important role in plaque instability. Methods: Using 99mTc-labeled broad-spectrum MMP inhibitor (MPI), we performed noninvasive imaging of MMP expression with micro-SPECT/micro-CT in mice deficient in apolipoprotein E (ApoE−/−, n = 14), mice deficient in low-density-lipoprotein receptor (LDLR−/−, n = 14), and C57/BL6 mice as controls (n = 7). Seven ApoE−/− and 7 LDLR−/− received a high-cholesterol diet. After in vivo imaging, aortas were explanted, ex vivo images acquired, and the percent injected dose of MPI per gram (%ID/g) determined, followed by histologic characterization of atherosclerotic lesions. Results: MPI uptake was noninvasively visualized in atherosclerotic lesions by micro-SPECT, with confirmation by micro-CT of anatomic location and aortic calcification. %ID/g in each part of the aorta was highest in ApoE−/− that were fed a high-cholesterol diet, followed by LDLR−/− that were fed a high-cholesterol diet, ApoE−/− that were fed normal chow, and LDLR−/− that were fed normal chow. The control mice had minimal MPI uptake. A significant correlation was noted between %ID/g and % area positive for macrophages (r = 0.81, P = 0.009), MMP-2 (r = 0.65, P = 0.013), and MMP-9 (r = 0.62, P = 0.008). Conclusion: This study demonstrates the usefulness of molecular imaging for noninvasive assessment of the extent of MMP expression in various transgenic mouse models of atherosclerosis receiving a normal or hyperlipidemic diet. It is conceivable that such a strategy may be translationally developed for identification of unstable atherosclerotic plaques.