title: Noninvasive detection of matrix metalloproteinase-9 in atherosclerotic lesions using technetium-99m-labeled single-photon emission computed tomography in vivo.
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 (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 Tc-McAb administration in vivo. Note that the radiochemistry purity of the Tc-McAb used was 85-95%. Biodistribution studies have shown that the clearance of Tc-McAb from blood was rapid. In addition, atherosclerotic lesions were clearly visualized on radioautography film shadows ex vivo.
  
  
  CONCLUSIONS
  MMP-9 activities within the atherosclerotic lesions were noninvasively detected using Tc-labeled SPECT in vivo.
authors.affiliation: aDepartment of Radiology, Nanjing Medical University Affiliated Wuxi Second Hospital bDepartment of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi cJiangsu Key Laboratory of Molecular and Function Imaging, Department of Radiology, Zhongda Hospital, Nanjing, China.
authors.forename: Zhongjuan
authors.initials: Z
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Deng
authors.forename: Zhuiyang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Huang
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000201:enzymology*; D001345:Autoradiography; D017536:Carotid Artery, Common / Q000201:enzymology; D004195:Disease Models, Animal; D005240:Feasibility Studies; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019275:Radiopharmaceuticals; D013667:Technetium; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D019275:Radiopharmaceuticals; D013667:Technetium; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse