Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle

Yingfeng Tu,1,2 Xiaowei Ma,3 Hao Chen,2,4 Yuhua Fan,5 Lei Jiang,2 Ruiping Zhang,2,6 Zhen Cheng2,4 1Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA; 3Department of Nuclear Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5College of Pharmacy, Harbin Medical University, Daqing, Heilongjiang, People’s Republic of China; 6The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, People’s Republic of ChinaCorrespondence: Zhen Cheng, Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, 1201 Welch Road, Lucas Expansion, P095, Stanford University, Stanford, CA, 94305, USA, Tel +01-650-723-7866, Email zcheng@simm.ac.cn Ruiping Zhang, Department of Radiology, the Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, People’s Republic of China, Email 1900547207@qq.comBackground: Matrix metalloproteinases from macrophages are important intraplaque components that play pivotal roles in plaque progression and regression. This study sought to develop a novel multifunctional positron emission tomography (PET) and magnetic resonance imaging (MRI) contrast agents based on MMP-2 cleavable nanoparticles to noninvasive assessment of MMP-2 activity in mouse carotid atherosclerotic plaques.Results: Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in CL57