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Systematic screening of potential beta-cell imaging agents.

Sweet, Ian R; Cook, Carla J.; Lernmark, Åke LU ; Greenbaum, Carla J.; Wallen, Angela R; Marcum, Erin S.; Stekhova, Svetlana A. and Krohn, Kenneth A. (2004) In Biochemical and Biophysical Research Communications 314(4). p.976-983
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... (More)
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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
314
issue
4
pages
976 - 983
publisher
Elsevier
external identifiers
  • scopus:0942289897
ISSN
1090-2104
DOI
10.1016/j.bbrc.2003.12.182
language
English
LU publication?
no
id
39e1ff0f-ae6d-4ff5-b826-d67a803f9aef (old id 1130257)
date added to LUP
2008-06-18 14:48:09
date last changed
2017-12-17 03:57:05
@article{39e1ff0f-ae6d-4ff5-b826-d67a803f9aef,
  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.},
  author       = {Sweet, Ian R and Cook, Carla J. and Lernmark, Åke and Greenbaum, Carla J. and Wallen, Angela R and Marcum, Erin S. and Stekhova, Svetlana A. and Krohn, Kenneth A.},
  issn         = {1090-2104},
  language     = {eng},
  number       = {4},
  pages        = {976--983},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Systematic screening of potential beta-cell imaging agents.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2003.12.182},
  volume       = {314},
  year         = {2004},
}