In vivo and ex vivo 19-fluorine magnetic resonance imaging and spectroscopy of beta-cells and pancreatic islets using GLUT-2 specific contrast agents.
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 of19FMHs in vivo with a temporal resolution of about 20 minutes, which showed a quick removal of19FMH from the circulation (within two hours). Ex vivo MR spectroscopy confirmed a preferential uptake of19FMH 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 of19F MRI need to be overcome. Copyright © 2016 John Wiley & Sons, Ltd.
Biomedical MRI unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Sayuan
S
Liang
Biomedical MRI unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.|Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Bruxelles, Belgium.
Karim
K
Louchami
Biomedical MRI unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Hauke
H
Kolster
Department of Chemistry, Faculty of Science, University of Hamburg, Hamburg, Germany.
Anna
A
Jacobsen
Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Bruxelles, Belgium.
Ying
Y
Zhang
Department of Chemistry, Faculty of Science, University of Hamburg, Hamburg, Germany.
Julian
J
Thimm
Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Bruxelles, Belgium.
Abdullah
A
Sener
Department of Chemistry, Faculty of Science, University of Hamburg, Hamburg, Germany.
Joachim
J
Thiem
Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Bruxelles, Belgium.
Willy
W
Malaisse
Biomedical MRI unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Tom
T
Dresselaers
Biomedical MRI unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Uwe
U
Himmelreich
D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D005461:Fluorine; D051273:Glucose Transporter Type 2 / Q000032:analysis* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000166:cytology*; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008356:Mannoheptulose / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D010179:Pancreas / Q000378:metabolism
D003287:Contrast Media; D051273:Glucose Transporter Type 2; C495680:SLC2A2 protein, human; D005461:Fluorine; D008356:Mannoheptulose
19F MRI; 19F MRS; GLUT-2 transporter; NMR; cell imaging; diabetes; mannoheptulose; pancreatic islets; β-cell mass; β-cells