Theranostics 2014; 4(8):787-797. doi:10.7150/thno.9525

Research Paper

Image-guided Pro-angiogenic Therapy in Diabetic Stroke Mouse Models Using a Multi-modal Nanoprobe

Ying-Ying Bai1, Xihui Gao2, Yuan-Cheng Wang1, Xin-Gui Peng1, Di Chang1, Shuyan Zheng2, Cong Li2✉, Shenghong Ju1✉

1. Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China;
2. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.

Abstract

Purpose: 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.

Keywords: angiogenesis, diabetes mellitus, endothelial progenitor cells, molecular imaging, nanoparticle, ischemic stroke.

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How to cite this article:
Bai YY, Gao X, Wang YC, Peng XG, Chang D, Zheng S, Li C, Ju S. Image-guided Pro-angiogenic Therapy in Diabetic Stroke Mouse Models Using a Multi-modal Nanoprobe. Theranostics 2014; 4(8):787-797. doi:10.7150/thno.9525. Available from http://www.thno.org/v04p0787.htm