title: Systematic screening of potential beta-cell imaging agents.
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.
authors.affiliation: Departments of Medicine, University of Washington, Seattle, WA 98195, USA. isweet@u.washington.edu
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sweet
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Cook
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: Angela R
authors.initials: AR
authors.lastname: Wallen
authors.forename: Erin S
authors.initials: ES
authors.lastname: Marcum
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Stekhova
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Krohn
mesh_terms: D000818:Animals; D007515:Islets of Langerhans / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011913:Rats, Inbred BB; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D019275:Radiopharmaceuticals