title: (19)F-heptuloses as tools for the non-invasive imaging of GLUT2-expressing cells.
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.
authors.affiliation: Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, Belgium. malaisse@ulb.ac.be
authors.forename: Willy J
authors.initials: WJ
authors.lastname: Malaisse
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Karim
authors.initials: K
authors.lastname: Louchami
authors.forename: Sonu
authors.initials: S
authors.lastname: Sharma
authors.forename: Tom
authors.initials: T
authors.lastname: Dresselaers
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.forename: Guy Wayne
authors.initials: GW
authors.lastname: Novotny
authors.forename: Thomas
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.forename: Daniel
authors.initials: D
authors.lastname: Waschke
authors.forename: Yevgeniy
authors.initials: Y
authors.lastname: Leshch
authors.forename: Julian
authors.initials: J
authors.lastname: Thimm
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiem
authors.forename: Abdullah
authors.initials: A
authors.lastname: Sener
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D005260:Female; D005461:Fluorine / Q000737:chemistry; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008356:Mannoheptulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D019047:Phantoms, Imaging; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051273:Glucose Transporter Type 2; D007328:Insulin; C495683:Slc2a2 protein, rat; D005461:Fluorine; D008356:Mannoheptulose