In vivo and ex vivo 19-fluorine magnetic resonance imaging and spectroscopy of beta-cells and pancreatic islets using GLUT-2 specific contrast agents

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• 作者：Sayuan Liang ; Karim Louchami ; Hauke Kolster ; Anna Jacobsen ; Ying Zhang ; Julian Thimm ; Abdullah Sener ; Joachim Thiem ; Willy Malaisse ; Tom Dresselaers and Uwe Himmelreich
• 刊名：Contrast Media & Molecular Imaging
• 出版年：2016
• 出版时间：November/December 2016
• 年：2016
• 卷：11
• 期：6
• 页码：506-513
• 全文大小：295K
• ISSN：1555-4317

文摘

The assessment of the β-cell mass in experimental models of diabetes and ultimately in patients is a hallmark to understand the relationship between reduced β-cell mass/function and the onset of diabetes. It has been shown before that the GLUT-2 transporter is highly expressed in both β-cells and hepatocytes and that D-mannoheptulose (DMH) has high uptake specificity for the GLUT-2 transporter. As 19-fluorine MRI has emerged as a new alternative method for MRI cell tracking because it provides potential non-invasive localization and quantification of labeled cells, the purpose of this project is to validate β-cell and pancreatic islet imaging by using fluorinated, GLUT-2 targeting mannoheptulose derivatives (¹⁹FMH) both in vivo and ex vivo. In this study, we confirmed that, similar to DMH, ¹⁹FMHs inhibit insulin secretion and increase the blood glucose level in mice temporarily (approximately two hours). We were able to assess the distribution of ¹⁹FMHs in vivo with a temporal resolution of about 20 minutes, which showed a quick removal of ¹⁹FMH from the circulation (within two hours). Ex vivo MR spectroscopy confirmed a preferential uptake of ¹⁹FMH in tissue with high expression of the GLUT-2 transporter, such as liver, endocrine pancreas and kidney. No indication of further metabolism was found. In summary, ¹⁹FMHs are potentially suitable for visualizing and tracking of GLUT-2 expressed cells. However, current bottlenecks of this technique related to the quick clearance of the compound and relative low sensitivity of ¹⁹F MRI need to be overcome. Copyright