RT Journal Article
SR Electronic
T1 Molecular Imaging of Matrix Metalloproteinase Expression in Atherosclerotic Plaques of Mice Deficient in Apolipoprotein E or Low-Density-Lipoprotein Receptor
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 612
OP 617
DO 10.2967/jnumed.108.055889
VO 50
IS 4
A1 Satoru Ohshima
A1 Artiom Petrov
A1 Shinichiro Fujimoto
A1 Jun Zhou
A1 Michael Azure
A1 D. Scott Edwards
A1 Toyoaki Murohara
A1 Navneet Narula
A1 Sotirios Tsimikas
A1 Jagat Narula
YR 2009
UL http://jnm.snmjournals.org/content/50/4/612.abstract
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.