title: Image-guided pro-angiogenic therapy in diabetic stroke mouse models using a multi-modal nanoprobe.
abstract: OBJECTIVE
  The efficacy of pro-angiogenic therapy is difficult to evaluate with current diagnostic modalities. The objectives were to develop a non-invasive imaging strategy to define the temporal characteristics of angiogenesis and to evaluate the response to pro-angiogenic therapy in diabetic stroke mouse models.
  
  
  METHODS
  A home-made ανβ3 integrin-targeted multi-modal nanoprobe was intravenously injected into mouse models at set time points after photothrombotic stroke. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging were carried out at 24 h post-injection. Bone marrow-derived endothelial progenitor cells (EPCs) were infused into the mouse models of ischemic stroke to stimulate angiogenesis.
  
  
  RESULTS
  The peak signal intensity in the ischemic-angiogenic area of diabetic and wild-type mouse models was achieved on day 10, with significantly lower signal enhancement observed in the diabetic models. Although the signal intensity was significantly higher after EPC treatment in both models, the enhancement was less pronounced in the diabetic animals compared with the wild-type controls. Histological analysis revealed that the microvessel density and expression of β3 integrin were correlated with the signal intensity assessed with MRI and NIRF imaging.
  
  
  CONCLUSIONS
  The non-invasive imaging method could be used for early and accurate evaluation of the response to pro-angiogenic therapy in diabetic stroke models.
authors: 1. Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China;
authors: Ying-Ying
authors: YY
authors: Bai
authors: 2. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors: Xihui
authors: X
authors: Gao
authors: 1. Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China;
authors: Yuan-Cheng
authors: YC
authors: Wang
authors: 1. Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China;
authors: Xin-Gui
authors: XG
authors: Peng
authors: 1. Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China;
authors: Di
authors: D
authors: Chang
authors: 2. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors: Shuyan
authors: S
authors: Zheng
authors: 2. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors: Cong
authors: C
authors: Li
authors: 1. Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China;
authors: Shenghong
authors: S
authors: Ju
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048909:Diabetes Complications / Q000628:therapy*; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D018919:Neovascularization, Physiologic; D013050:Spectrometry, Fluorescence; D020521:Stroke / Q000150:complications* / Q000628:therapy*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D039564:Integrin alphaV; D039661:Integrin beta3
keywords: angiogenesis; diabetes mellitus; endothelial progenitor cells; ischemic stroke.; molecular imaging; nanoparticle