Systematic screening of potential beta-cell imaging agents.

Research output: Contribution to journalArticle

Abstract

The beta-cell loss seen in diabetes mellitus could be monitored clinically by positron emission tomography (PET) if imaging agents were sufficiently specific for beta-cells to overcome the high ratio of non-beta-cell to beta-cell tissue in pancreas. In this report, we present a screening assay for identifying beta-cell-specific compounds that is based on the relative accumulation and retention by islet, INS-1, and exocrine (PANC-1) cells of candidate molecules. Molecules thought to have a high affinity for beta-cells were tested and included glibenclamide, tolbutamide, serotonin, L-DOPA, dopamine, nicotinamide, fluorodeoxyglucose, and fluorodithizone. Glibenclamide and fluorodithizone were the most specific, but the specificity ratios fell well below those needed to attain robust signal to background ratio as a PET imaging agent for quantifying beta-cell mass. In vivo tests of the biodistribution of glibenclamide and fluorodithizone in rats indicated that the compounds were not specifically associated with pancreas, bearing out the predictions of the in vitro screen.

Details

Authors
  • Ian R Sweet
  • Carla J. Cook
  • Åke Lernmark
  • Carla J. Greenbaum
  • Angela R Wallen
  • Erin S. Marcum
  • Svetlana A. Stekhova
  • Kenneth A. Krohn
External organisations
  • University of Washington, Seattle
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences
Original languageEnglish
Pages (from-to)976-983
JournalBiochemical and Biophysical Research Communications
Volume314
Issue number4
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes