Atherosclerosis Plaque Heterogeneity and Response to Therapy Detected by In Vivo Molecular Imaging of Matrix Metalloproteinase Activation
| Autor: | Lei Nie, Mahmoud Razavian, Lawrence W. Dobrucki, Sina Tavakoli, Simon P. Robinson, Albert J. Sinusas, Mehran M. Sadeghi, Jiasheng Zhang, Michael Azure |
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| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Time Factors Matrix metalloproteinase Diet High-Fat Multimodal Imaging Article Mice chemistry.chemical_compound Apolipoproteins E In vivo medicine.artery medicine Animals Oil Red O Macrophage Radiology Nuclear Medicine and imaging Radioactive Tracers Aorta medicine.diagnostic_test Biological Transport Matrix Metalloproteinases Plaque Atherosclerotic Molecular Imaging Staining Enzyme Activation Treatment Outcome chemistry Positron emission tomography Positron-Emission Tomography Female Tomography X-Ray Computed Preclinical imaging |
| Zdroj: | Journal of Nuclear Medicine. 52:1795-1802 |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.111.092379 |
| Popis: | Matrix metalloproteinases (MMPs) play a key role in the development of atherosclerosis and its complications. In vivo detection and quantification of MMP activation can help track the propensity to complications and response to therapy. We sought to establish an in vivo imaging approach for monitoring MMP activation in atherosclerotic mouse aorta and use it to assess the response to dietary modification. Method: Apolipoprotein-deficient mice were fed normal chow or a high-fat diet (HFD) for up to 3 mo or a HFD for 2 mo, followed by 1 mo on normal chow. Then they underwent micro-SPECT/CT, along with autoradiography and oil red O staining of tissues. Results: After 3 mo of HFD, there was considerable atherosclerosis in the aorta. In vivo micro-SPECT/CT using RP782 (an 111In-labeled tracer targeting activated MMPs) showed a heterogeneous pattern of tracer uptake along the aorta. Heterogeneity of RP782 uptake was confirmed by autoradiography, and specificity was demonstrated using excess unlabeled precursor. Tracer uptake quantified by micro-SPECT significantly correlated with uptake quantified by autoradiography. Comparison of oil red O staining with autoradiography demonstrated areas of discordance between plaque presence and tracer uptake. HFD withdrawal led to significant reduction in RP782 uptake beyond the effect on plaque area. MMP expression and macrophage infiltration were similarly heterogeneous along the aorta and significantly reduced after withdrawal from the HFD. Finally, RP782 uptake significantly correlated with aortic macrophage content. Conclusion: Molecular imaging of MMP activation reveals the heterogeneity of atherosclerotic plaques and is a useful tool for tracking plaque biology and response to therapy. |
| Databáze: | OpenAIRE |
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