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

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

15 Citations (Scopus)

Abstract

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 (19)F-heptuloses could be used for non-invasive imaging of GLUT2-expressing cells. After 20 min incubation, the uptake of (19)F-heptuloses (25 mM) by rat hepatocytes, as assessed by (19)F NMR spectroscopy, ranged from 0.50 (1-deoxy-1-fluoro-d-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) µmol per 3×10(6)cells. (19)F MRI experiments also allowed the detection of 1-deoxy-1-fluoro-d-mannoheptulose in rat hepatocytes. All three (19)F-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 10mM d-glucose to the same extent as that observed with an equivalent concentration (10mM) of d-mannoheptulose, while 3-deoxy-3-fluoro-d-glucoheptulose and 1,3-dideoxy-1,3-difluoro-d-glucoheptulose (also 10mM) were less potent than d-mannoheptulose in inhibiting insulin release. The 1-deoxy-1-fluoro-d-mannoheptulose and 3-deoxy-3-fluoro-d-mannoheptulose only marginally affected INS-1 cell viability. These findings are compatible with the view that selected (19)F-heptuloses may represent suitable tools for the non-invasive imaging of hepatocytes and insulin-producing cells by (19)F MRI.
Original languageEnglish
JournalArchives of Biochemistry and Biophysics
Volume517
Issue number2
Pages (from-to)138-43
Number of pages6
ISSN1096-0384
DOIs
Publication statusPublished - 15 Jan 2012

Keywords

  • Animals
  • Cell Line
  • Cell Survival
  • Female
  • Fluorine
  • Glucose Transporter Type 2
  • Hepatocytes
  • Insulin
  • Islets of Langerhans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Mannoheptulose
  • Phantoms, Imaging
  • Rats
  • Rats, Wistar

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