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• W7763629 abstract "248 Objectives Development of treatments to prevent or restore islet β-cell mass (BCM) in diabetic patients is hampered by a lack of robust methods for the non-invasive imaging of BCM. Using the LifeSpan DrugTargetTM Database we identified mGluR5 as a potential candidate target for BCM imaging. We report here the determination of mGluR5 specificity to pancreatic islets via immunohistochemistry, in vitro radioligand binding and in vivo PET imaging studies in diabetic rat models. Methods Immunohistochemistry of formalin-fixed paraffin-embedded human tissues and cell lines were used to determine the tissue specificity of mGluR5. Binding and uptake of mGluR5 radioligands by the rat insulinoma cell line (INS-1) and isolated rat islets and pancreatic exocrine cell line (PANC-1) were compared. PET imaging studies were carried out in SD rats (5 control, 3 streptozotocin [STZ] treated) using HRRT following 0.33±0.07 mCi [18F]FPEB (a selective mGluR5 ligand). Time activity curves (TACs) were obtained from the pancreas, liver, and kidney cortex. Animals were sacrificed and pancreases were assayed for insulin content after imaging. Results Using a standard pathology grading scale of 0-4, mGluR5 was determined to be maximally present in pancreatic islets (score=4), but non-detectable in either the pancreatic acinar (score=0), or ductal (score=0) cells. PET imaging with high specific activity [18F]FPEB showed that SUV in pancreas peaked at 30-50 min, and plateaued by 90 min until the end of image acquisition (180 min). FPEB pancreatic SUV reasonably correlated with post-mortem measures of insulin content. In comparison to similar studies using VMAT2 ligands ([11C]DTBZ or [18F]FP-DTBZ), the slope of the correlation of FPEB SUV with pancreatic insulin was ~2.7-fold greater; in addition, a reduced background binding (by ~80%) was seen for FPEB. Conclusions These results suggest that mGluR5 may be a potential biomarker, and [18F]FPEB may represent an improved PET-ligand for imaging pancreatic β-cell mass. Research Support JDR" @default.
• W7763629 created "2016-06-24" @default.
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• W7763629 date "2010-05-01" @default.
• W7763629 modified "2023-09-24" @default.
• W7763629 title "PET imaging of mGluR5 receptor as a potential biomarker to measure pancreatic beta-cell mass" @default.
• W7763629 hasPublicationYear "2010" @default.
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