Back to Search
Start Over
Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor Agonists as PET Tracers for Pancreatic β cell Imaging.
- Source :
-
Molecular imaging and biology [Mol Imaging Biol] 2016 Feb; Vol. 18 (1), pp. 90-8. - Publication Year :
- 2016
-
Abstract
- 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).<br />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.<br />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.<br />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.
- Subjects :
- Animals
Autoradiography
Exenatide
Glucagon-Like Peptide-1 Receptor metabolism
Heterocyclic Compounds, 1-Ring chemistry
Male
Peptides chemistry
Rats, Sprague-Dawley
Signal Processing, Computer-Assisted
Tissue Distribution
Tomography, X-Ray Computed
Venoms chemistry
Vinyl Compounds chemistry
Copper Radioisotopes metabolism
Gallium Radioisotopes metabolism
Glucagon-Like Peptide-1 Receptor agonists
Insulin-Secreting Cells diagnostic imaging
Molecular Imaging methods
Positron-Emission Tomography methods
Radiopharmaceuticals metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1860-2002
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular imaging and biology
- Publication Type :
- Academic Journal
- Accession number :
- 25987465
- Full Text :
- https://doi.org/10.1007/s11307-015-0861-5