Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with 99mTc-DTPA-glipizide

This study was aimed to assess pancreas beta cell activity using Tc-99m-diethyleneaminepentaacetic acid-glipizide (DTPA-GLP), a sulfonylurea receptor agent. The effect of DTPA-GLP on the blood glucose level in rats was also evaluated. 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 Tc-99m-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 Tc-99m-DTPA. To demonstrate pancreas beta cell uptake of Tc-99m-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. The structure of DTPA-GLP was confirmed by NMR, mass spectrometry and HPLC. Radiochemical purity assessed by ITLC was > 96%. Tc-99m-DTPA-GLP showed increased pancreas-to-muscle ratios, whereas Tc-99m-DTPA showed decreased ratios at various time points. Pancreas could be visualized with Tc-99m-DTPA-GLP in normal rat, however, Tc-99m-DTPA has poor uptake suggesting the specificity of Tc-99m-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. It is feasible to use Tc-99m-DTPA-GLP to assess pancreas beta cell receptor recognition. Tc-99m-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors.