F-19-heptuloses as tools for the non-invasive imaging of GLUT2-expressing cells

作者：Malaisse Willy J^*; Zhang Ying; Louchami Karim; Sharma Sonu; Dresselaers Tom; Himmelreich Uwe; Novotny Guy Wayne; Mandrup Poulsen Thomas; Waschke Daniel; Leshch Yevgeniy; Thimm Julian; Thiem Joachim; Sener Abdullah

来源：Archives of Biochemistry and Biophysics, 2012, 517(2): 138-143.

DOI：10.1016/j.abb.2011.11.014

• F-19-heptuloses
• GLUT2-expressing cells
• Rat hepatocytes
• Insulin secretion
• Rat pancreatic islets

Suitable analogs of D-mannoheptulose are currently considered as possible tools for the non-invasive imaging of pancreatic islet insulin-producing cells. Here, we examined whether F-19-heptuloses could be used for non-invasive imaging of GLUT2-expressing cells. After 20 min incubation, the uptake of F-19-heptuloses (25 mM) by rat hepatocytes, as assessed by F-19 NMR spectroscopy, ranged from 0.50 (1-deoxy-1-fluoro-o-mannoheptulose and 3-deoxy-3-fluoro-D-mannoheptulose) to 0.25 (1,3-dideoxy-1, 3-difluoro-D-mannoheptulose) and 0.13 (1-deoxy-1-fluoro-D-glucoheptulose, 3-deoxy-3-fluoro-D-glucoheptulose and 1,3-dideoxy-1,3-difluoro-D-glucoheptulose) mu mol per 3 x 10(6) cells. F-19 MRI experiments also allowed the detection of 1-deoxy-1-fluoro-D-mannoheptulose in rat hepatocytes. All three F-19-mannoheptuloses cited above, as well as 7-deoxy-7-fluoro-D-mannoheptulose and 1-deoxy-1-fluoro-D-glucoheptulose inhibited insulin release evoked in rat isolated pancreatic islets by 10 mM D-glucose to the same extent as that observed with an equivalent concentration (10 mM) of D-mannoheptulose, while 3-deoxy-3-fluoro-D-glucoheptulose and 1,3-dideoxy-1,3-difluoro-D-glucoheptulose (also 10 mM) were less potent than D-mannoheptulose in inhibiting insulin release. The 1-deoxy-1-fluoroD-mannoheptulose and 3-deoxy-3-fluoro-D-mannoheptulose only marginally affected INS-1 cell viability. These findings are compatible with the view that selected F-19-heptuloses may represent suitable tools for the non-invasive imaging of hepatocytes and insulin-producing cells by F-19 MRI.

• 出版日期2012-1-15