Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with 99mTc-DTPA-glipizide
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This study was aimed to assess pancreas beta cell activity using 99mTc-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 99mTc-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 99mTc-DTPA. To demonstrate pancreas beta cell uptake of 99mTc-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%. 99mTc-DTPA-GLP showed increased pancreas-to-muscle ratios, whereas 99mTc-DTPA showed decreased ratios at various time points. Pancreas could be visualized with 99mTc-DTPA-GLP in normal rat, however, 99mTc-DTPA has poor uptake suggesting the specificity of 99mTc-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 99mTc-DTPA-GLP to assess pancreas beta cell receptor recognition. 99mTc-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors.
Keywords99mTc-DTPA-glipizide Sulfonylurea receptor Imaging Pancreas
This work was supported in part by MDA Sponsored Research Grant (SR 2002-00007147SM, MDACC), by Cell>Point LLC Biotechnology (Englewood, CO), by a grant of ICSR (CNUHRICM-U-200518, Korea) and the John S. Dunn Foundation. The chemistry and animal research are supported by M.D. Anderson Cancer Center (CORE) Grant NIH CA-16672.
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