Systematic screening of potential β-cell imaging agents

Ian R. Sweet, Daniel L. Cook, Åke Lernmark, Carla J. Greenbaum, Angela R. Wallen, Erin S. Marcum, Svetlana A. Stekhova, Kenneth Krohn

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

The β-cell loss seen in diabetes mellitus could be monitored clinically by positron emission tomography (PET) if imaging agents were sufficiently specific for β-cells to overcome the high ratio of non-β-cell to β-cell tissue in pancreas. In this report, we present a screening assay for identifying β-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 β-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 β-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.

Original languageEnglish (US)
Pages (from-to)976-983
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume314
Issue number4
DOIs
StatePublished - Feb 20 2004
Externally publishedYes

Fingerprint

Glyburide
Screening
Positron emission tomography
Imaging techniques
Bearings (structural)
Tolbutamide
Molecules
Niacinamide
Medical problems
Rats
Assays
Dopamine
Serotonin
Positron-Emission Tomography
Tissue
Pancreas
Diabetes Mellitus

Keywords

  • β-Cell mass
  • Dithizone
  • Fluorodithizone
  • Glibenclamide
  • Pancreatic imaging agent
  • PET
  • Screening assay

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Sweet, I. R., Cook, D. L., Lernmark, Å., Greenbaum, C. J., Wallen, A. R., Marcum, E. S., ... Krohn, K. (2004). Systematic screening of potential β-cell imaging agents. Biochemical and Biophysical Research Communications, 314(4), 976-983. https://doi.org/10.1016/j.bbrc.2003.12.182

Systematic screening of potential β-cell imaging agents. / Sweet, Ian R.; Cook, Daniel L.; Lernmark, Åke; Greenbaum, Carla J.; Wallen, Angela R.; Marcum, Erin S.; Stekhova, Svetlana A.; Krohn, Kenneth.

In: Biochemical and Biophysical Research Communications, Vol. 314, No. 4, 20.02.2004, p. 976-983.

Research output: Contribution to journalArticle

Sweet, IR, Cook, DL, Lernmark, Å, Greenbaum, CJ, Wallen, AR, Marcum, ES, Stekhova, SA & Krohn, K 2004, 'Systematic screening of potential β-cell imaging agents', Biochemical and Biophysical Research Communications, vol. 314, no. 4, pp. 976-983. https://doi.org/10.1016/j.bbrc.2003.12.182
Sweet IR, Cook DL, Lernmark Å, Greenbaum CJ, Wallen AR, Marcum ES et al. Systematic screening of potential β-cell imaging agents. Biochemical and Biophysical Research Communications. 2004 Feb 20;314(4):976-983. https://doi.org/10.1016/j.bbrc.2003.12.182
Sweet, Ian R. ; Cook, Daniel L. ; Lernmark, Åke ; Greenbaum, Carla J. ; Wallen, Angela R. ; Marcum, Erin S. ; Stekhova, Svetlana A. ; Krohn, Kenneth. / Systematic screening of potential β-cell imaging agents. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 314, No. 4. pp. 976-983.
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