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

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

“…However, the difficulties of visualizing the 19 FMH taken up by hepatocytes or ß cells in vivo not only results from the low fluorine content of 19 FMH itself, but also comes from the small portion of 19 FMH taken up by these cells and its subsequent rapid clearance of the compound from the circulation system. In previous in vitro experiments, it was shown that isolated islets incubated with FMHs for 24 hours show good uptake of FMH by ß cells (15), which is further evidence that the short circulation time of FMH hinders its application for in vivo 19 F MRI. We were able to confirm these previous cell experiments by ex vivo 19 F MRS of excised liver and pancreas tissue.…”

“…The detection limit for 19 F MRI is approximately 5*10 15 F spins/pixel using a gradient echo 3D sequence with 120 averages and a similar repetition time of 1 s, which is in a similar range (10 15 -10 16 ) as described in the literature (16,17 19 FMH by isolated islets. Considering an islet diameter of 200 to 400 μm (18,19), the intra-islet concentration averages 0.5 to 4 M after overnight incubation of islets at 37°C in the presence of 15 mM of [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] FMH (see also Figure 3). This was based on a measured average 18 nmol 19 F spins per islet.…”

“…Hence, these compounds are potential agents for β-cell imaging after synthesizing 19 F containing deoxy-DMH, which can be detected by 19 F MRI and further used for cell imaging after their In vitro 3-19 FMH uptake by isolated islets: (A) Extra-islet and intra-islet concentration of 19 F spins after 24 hours incubation with 15 mM entrapment in those cells (13,14). Initial in vitro studies on the uptake of different 19 F-deoxyfluoromannoheptuloses ( 19 FMH) by rat hepatocytes and their effects upon glucose-induced insulin release from isolated rat pancreatic islets have already been successful in a proof-of-concept study (15). The current study will mainly focus on the in vivo application of 19 FMHs and 19 F deoxyfluoroglucose (FDG) (see Figure 1) and its validation following systematic injection and the assessment of its feasibility to quantify GLUT-2 expressing cells.…”

CHAPTER 11. Magnetic Resonance‐Based Cell Imaging Using Contrast Media and Reporter Genes

“…Malaisse et al have used fluorinated mannoheptuloses that are specifically taken up by the glucose transporter-2 (GLUT2) of hepatocytes and pancreatic cells. 106,107 In vitro 19 F MRI experiments have indicated detectability limits in the order of thousands of cells per microliter. The in vivo applicability of this approach remains to be proven.…”

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

“…Accordingly, ketoheptoses and fluorinated ketoheptoses were considered to be potential therapeutic agents for hypoglycemia and cancer as well as diagnostic tools for diabetes [7–12]. Amino- and azido-group-containing ketoheptoses were also synthesized for the development of novel antibiotics and the evaluation of carbohydrate–lectin interactions by conjugation with fluorescent quantum dots via click chemistry [13–14].…”