title: Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with (99m)Tc-DTPA-glipizide.
abstract: OBJECTIVE
  This study was aimed to assess pancreas beta cell activity using (99m)Tc-diethyleneaminepentaacetic acid-glipizide (DTPA-GLP), a sulfonylurea receptor agent. The effect of DTPA-GLP on the blood glucose level in rats was also evaluated.
  
  
  METHODS
  DTPA dianhydride was conjugated with GLP in the presence of sodium amide, yielding 60%. Biodistribution and planar images were obtained at 30-120 min after injection of (99m)Tc-DTPA-GLP (1 mg/rat, 0.74 and 11.1 MBq per rat, respectively) in normal female Fischer 344 rats. The control group was given (99m)Tc-DTPA. To demonstrate pancreas beta cell uptake of (99m)Tc-DTPA-GLP via a receptor-mediated process, a group of rats was pretreated with streptozotocin (a beta cell toxin, 55 mg/kg, i.v.) and the images were acquired at immediately-65 min on day 5 post-treatment. The effect on the glucose levels after a single administration (ip) of DTPA-GLP was compared to glipizide (GLP) for up to 6 h.
  
  
  RESULTS
  The structure of DTPA-GLP was confirmed by NMR, mass spectrometry and HPLC. Radiochemical purity assessed by ITLC was >96%. (99m)Tc-DTPA-GLP showed increased pancreas-to-muscle ratios, whereas (99m)Tc-DTPA showed decreased ratios at various time points. Pancreas could be visualized with (99m)Tc-DTPA-GLP in normal rat, however, (99m)Tc-DTPA has poor uptake suggesting the specificity of (99m)Tc-DTPA-GLP. Pancreas beta cell uptake could be blocked by pre-treatment with streptozotocin. DTPA-GLP showed an equal or better response in lowering the glucose levels compared to the existing GLP drug.
  
  
  CONCLUSIONS
  It is feasible to use (99m)Tc-DTPA-GLP to assess pancreas beta cell receptor recognition. (99m)Tc-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors.
authors.affiliation: Division of Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chang-Sok
authors.initials: CS
authors.lastname: Oh
authors.forename: Saady
authors.initials: S
authors.lastname: Kohanim
authors.forename: Fan-Lin
authors.initials: FL
authors.lastname: Kong
authors.forename: Ho-Chun
authors.initials: HC
authors.lastname: Song
authors.forename: Nathan
authors.initials: N
authors.lastname: Huynh
authors.forename: Richard
authors.initials: R
authors.lastname: Mendez
authors.forename: Mithu
authors.initials: M
authors.lastname: Chanda
authors.forename: E
authors.initials: E
authors.lastname: Edmund Kim
authors.forename: David J
authors.initials: DJ
authors.lastname: Yang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002614:Chelating Agents / Q000737:chemistry; D005260:Female; D005913:Glipizide / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D057054:Molecular Imaging / Q000379:methods*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011854:Radiochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D064233:Sulfonylurea Receptors; D016284:Technetium Tc 99m Pentetate / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D002614:Chelating Agents; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D016284:Technetium Tc 99m Pentetate; D005913:Glipizide