Noninvasive detection of matrix metalloproteinase-9 in atherosclerotic lesions using technetium-99m-labeled single-photon emission computed tomography in vivo. Issue 4 (April 2017)

• Record Type: Journal Article
• Authors: Wang, Zhongjuan; Deng, Gang; Zhang, Zhuiyang; Huang, Hongbo; Zhao, Yanjun
• Is Part Of: Nuclear medicine communications. Volume 38:Issue 4(2017:Apr.)
• Publication Date: 2017-04
• Subjects: atherosclerosis -- matrix metalloproteinase-9 -- mice -- single-photon emission computed tomography; Nuclear medicine -- Periodicals; 616.07575
• DOI: 10.1097/MNM.0000000000000651
• Languages: English
• ISSNs: 0143-3636

Abstract

Abstract : Objective: Previous studies have suggested that matrix metalloproteinase (MMP) inhibitor uptake may offer a precise estimation of MMP activity in atherosclerotic lesions. In this study, we explored the feasibility of noninvasive detection of MMP-9 activity using technetium-99m-labeled matrix metalloproteinase-9 antibody ( 99m Tc-McAb) in vivo . Methods: ApoE-deficient (ApoE −/− ) atherosclerosis mice models ( n =10) were induced through a high-cholesterol diet following ligation of their left common carotid artery. After 4 weeks, the models were verified through proton density-weighted and T2-weighted images obtained by MRI. C57BL/6 sham mice ( n =8) were used as controls. In addition, normal mice ( n =20) were used to characterize blood clearance. After radiolabeled McAb administration, single-photon emission computed tomography (SPECT) was performed. Subsequently, left common carotid arteries were harvested for ex-vivo autoradiograph imaging. Then, morphology and activity assays of MMP-9 were histologically and immunohistochemically examined. Results: MRI showed higher signal intensities in the left common carotid arteries with irregular stenoses in the lumen of blood vessels in atherosclerosis mice models in vivo . Atherosclerotic lesions on left common carotid artery specimens were also clearly visualized using SPECT 2 h after 99m Tc-McAb administration in vivo . Note that the radiochemistry purity of the 99m Tc-McAb used was 85–95%. Biodistribution studies have shown that the clearance of 99m Tc-McAb from blood was rapid. In addition, atherosclerotic lesions were clearly visualized on radioautography film shadows ex vivo . Conclusion: MMP-9 activities within the atherosclerotic lesions were noninvasively detected using 99m Tc-labeled SPECT in vivo .