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Exp Clin Endocrinol Diabetes 2005; 113(7): 388-395
DOI: 10.1055/s-2005-865711
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

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

S. Schneider[*] 1 , P. J. Feilen2 , M. Schreckenberger3 , M. Schwanstecher4 , C. Schwanstecher4 , H. G. Buchholz3 , O. Thews5 , K. Oberholzer6 , A. Korobeynikov7 , A. Bauman7 , S. Comagic7 , M. Piel7 , E. Schirrmacher[*] 3 , C. Y. Shiue8 , A. A. Alavi8 , P. Bartenstein3 , F. Rösch7 , M. M. Weber2 , H. H. Klein1 , R. Schirrmacher3
  • 1Medical Department I, University Hospital Bergmannsheil, University of Bochum, Bochum, Germany
  • 2Division of Endocrinology and Metabolism, I. Medical Department, University of Mainz, Mainz, Germany
  • 3Department of Nuclear Medicine, University of Mainz, Mainz, Germany
  • 4Institute of Pharmacology and Toxicology, University of Braunschweig, Braunschweig, Germany
  • 5Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany
  • 6Department of Radiology, University of Mainz, Mainz, Germany
  • 7Institute of Nuclear Chemistry, University of Mainz, Mainz, Germany
  • 8Department of Radiology, University of Pennsylvania, Philadelphia, USA
Further Information

Publication History

Received: July 6, 2004 First decision: September 20, 2004

Accepted: May 2, 2005

Publication Date:
18 July 2005 (online)

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Abstract

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 99mTc-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 mTc-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.

Key words

Glibenclamide derivatives - pancreatic islet cell mass - sulfonylurea receptor 1

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1 Both authors contributed equally.

Dr. Stephan Schneider

Medical Department I
University Hospital Bergmannsheil
Bürkle-de-la-Camp-Platz 1
44789 Bochum
Germany

Phone: + 492343023469

Fax: + 49 23 43 02 64 03

Email: Stephan.Schneider@ruhr-uni-bochum.de

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