In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans
| Autor: | S. Comagic, Mathias Schreckenberger, Frank Rösch, Esther Schirrmacher, K. Oberholzer, Oliver Thews, M. Schwanstecher, Andreas Bauman, Peter Bartenstein, Harald Klein, Markus Piel, C. Schwanstecher, A. Korobeynikov, P. J. Feilen, Abass Alavi, Stephan Schneider, Ralf Schirrmacher, Hans-Georg Buchholz, C. Y. Shiue, Matthias M. Weber |
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| Rok vydání: | 2005 |
| Předmět: |
Fluorine Radioisotopes
Potassium Channels Endocrinology Diabetes and Metabolism medicine.medical_treatment Receptors Drug Sulfonylurea Receptors Glibenclamide Rats Sprague-Dawley Islets of Langerhans Endocrinology In vivo Glyburide Internal Medicine medicine Diabetes Mellitus Animals Humans Hypoglycemic Agents Insulin Potassium Channels Inwardly Rectifying Receptor Chemistry Technetium General Medicine Magnetic Resonance Imaging Rats medicine.anatomical_structure Biochemistry Positron-Emission Tomography Lipophilicity Sulfonylurea receptor ATP-Binding Cassette Transporters Radiopharmaceuticals Pancreas Drug metabolism medicine.drug |
| Zdroj: | Experimental and clinical endocrinologydiabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 113(7) |
| ISSN: | 0947-7349 |
| Popis: | Pancreatic islet cell mass (PICM) is a major determinant of the insulin secretory capacity in humans. Currently, the only method for accurate assessment of the PICM is an autopsy study. Thus, development of a technique allowing the non-invasive quantification of PICM is of great interest. The aim of this study was to develop such a non-invasive technique featuring novel fluorine- and (99m)Tc-labelled glibenclamide derivatives. Despite the structural modifications necessary to introduce fluorine into the glibenclamide molecule, all derivatives retained insulin stimulating capacity as well as high affinity binding to human SUR1 when compared to the original glibenclamide. Contrastingly, the lipophilicity of the fluorine-labelled derivatives was altered depending on the particular modification. In the human PET-study a constant but weak radioactive signal could be detected in the pancreas using a fluorine-labelled glibenclamide derivative. However, a reliable assessment and visualisation of the PICM could not be obtained. It can be assumed that the high uptake of the fluorine-labelled tracer e.g. into the the liver and the high plasma protein binding leads to a relatively low signal-to-noise ratio. In case of the presented fluorine-labelled glibenclamide based compounds this could be the result of their invariably high lipophilicity. The development of a (99 m)Tc-labelled glibenclamide derivative with a lower lipophilicity and differing in vivo behaviour, glibenclamide based compounds for non-invasive imaging of the pancreatic islet cell mass may be possible. |
| Databáze: | OpenAIRE |
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