Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor Agonists as PET Tracers for Pancreatic β cell Imaging.

Academic Article


  • PURPOSE: Copper-64 (Cu-64) and Galium-68 (Ga-68) radiolabeled DO3A and NODA conjugates of exendin-4 were used for preclinical imaging of pancreatic β cells via targeting of glucagon-like peptide-1 receptor (GLP-1R). PROCEDURES: DO3A-VS- and NODA-VS-tagged Cys(40)exendin-4 (DO3A-VS-Cys(40)-exendin-4 and NODA-VS-Cys(40)-exendin-4, respectively) were labeled with Cu-64 and Ga-68 using standard techniques. Biodistribution and dynamic positron emission tomography (PET) were carried out in normal Sprague-Dawley (SD) rats. Ex vivo autoradiography imaging was conducted with freshly frozen pancreatic thin sections. RESULTS: DO3A-VS- and NODA-VS-Cys(40)-exendin-4 analogues were labeled with Cu-64 and Ga-68 to a specific activity of 518.7 ± 3.7 Ci/mmol (19.19 ± 0.14 TBq/mmol) and radiochemical yield above 98 %. Biodistribution data demonstrated pancreatic uptake of 0.11 ± 0.02 %ID/g for [(64)Cu]DO3A-VS-, 0.14 ± 0.02 %ID/g for [(64)Cu]NODA-VS-, 0.11 ± 0.03 for [(68)Ga]DO3A-VS-, and 0.26 ± 0.03 for [(68)Ga]NODA-VS-Cys(40)-exendin-4. Excess exendin-4 and exendin-(9-39)-amide displaced all four Cu-64 and Ga-68 labeled exendin-4 derivatives in blocking studies. CONCLUSIONS: [(64)Cu]/[(68)Ga]DO3A-VS-Cys(40)- and [(64)Cu]/[(68)Ga]NODA-VS-Cys(40)-exendin-4 can be used as PET imaging agents specific for GLP-1R expressed on β cells. Here, we report the first evidence of pancreatic uptake visualized with exendin-4 derivative in a rat animal model via in vivo dynamic PET imaging.
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  • Cu-64, Exendin-4, GLP-1, GLP-1R, Ga-68, PET, Pancreatic β cells, β cell mass, Animals, Autoradiography, Copper Radioisotopes, Exenatide, Gallium Radioisotopes, Glucagon-Like Peptide-1 Receptor, Heterocyclic Compounds, 1-Ring, Insulin-Secreting Cells, Male, Molecular Imaging, Peptides, Positron-Emission Tomography, Radiopharmaceuticals, Rats, Sprague-Dawley, Signal Processing, Computer-Assisted, Tissue Distribution, Tomography, X-Ray Computed, Venoms, Vinyl Compounds
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  • Bandara N; Zheleznyak A; Cherukuri K; Griffith DA; Limberakis C; Tess DA; Jianqing C; Waterhouse R; Lapi SE
  • Start Page

  • 90
  • End Page

  • 98
  • Volume

  • 18
  • Issue

  • 1