Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor Agonists as PET Tracers for Pancreatic β cell Imaging
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). PROCEDURES: DO3A-VS- and NODA-VS-tagged Cys40exendin-4 (DO3A-VS-Cys40-exendin-4 and NODA-VS-Cys40-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-Cys40-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 [64Cu]DO3A-VS-, 0.14 ± 0.02 %ID/g for [64Cu]NODA-VS-, 0.11 ± 0.03 for [68Ga]DO3A-VS-, and 0.26 ± 0.03 for [68Ga]NODA-VS-Cys40-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: [64Cu]/[68Ga]DO3A-VS-Cys40- and [64Cu]/[68Ga]NODA-VS-Cys40-exendin-4 can be used as PET imaging agents specific for GLP-1R expressed on β cells. Here in this paper, we report the first evidence of pancreatic uptake visualized with exendin-4 derivative in a rat animal model via in vivo dynamic PET imaging.
- Authors:
-
- Washington Univ. School of Medicine, St. Louis, MO (United States). Dept. of Radiology
- Pfizer Worldwide Research and Development, Cambridge, MA (United States). Worldwide Medicinal Chemistry
- Pfizer Worldwide Research and Development, Groton, CT (United States). Worldwide Medicinal Chemistry
- Pfizer Worldwide Research and Development, Cambridge, MA (United States). Pharmacokinetics, Dynamics and Metabolism
- Pfizer Worldwide Research and Development, Cambridge, MA (United States). Clinical and Translational Imaging
- Publication Date:
- Research Org.:
- The Washington Univ., St. Louis, MO (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1467465
- Grant/Contract Number:
- SC0002032
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Molecular Imaging and Biology
- Additional Journal Information:
- Journal Volume: 18; Journal Issue: 1; Journal ID: ISSN 1536-1632
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 62 RADIOLOGY AND NUCLEAR MEDICINE; GLP-1; GLP-1R; Pancreatic β cells; β cell mass; Exendin-4; PET; Cu-64; Ga-68
Citation Formats
Bandara, Nilantha, Zheleznyak, Alex, Cherukuri, Kaavya, Griffith, David A., Limberakis, Chris, Tess, David A., Jianqing, Chen, Waterhouse, Rikki, and Lapi, Suzanne E. Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor Agonists as PET Tracers for Pancreatic β cell Imaging. United States: N. p., 2015.
Web. doi:10.1007/s11307-015-0861-5.
Bandara, Nilantha, Zheleznyak, Alex, Cherukuri, Kaavya, Griffith, David A., Limberakis, Chris, Tess, David A., Jianqing, Chen, Waterhouse, Rikki, & Lapi, Suzanne E. Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor Agonists as PET Tracers for Pancreatic β cell Imaging. United States. https://doi.org/10.1007/s11307-015-0861-5
Bandara, Nilantha, Zheleznyak, Alex, Cherukuri, Kaavya, Griffith, David A., Limberakis, Chris, Tess, David A., Jianqing, Chen, Waterhouse, Rikki, and Lapi, Suzanne E. Tue .
"Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor Agonists as PET Tracers for Pancreatic β cell Imaging". United States. https://doi.org/10.1007/s11307-015-0861-5. https://www.osti.gov/servlets/purl/1467465.
@article{osti_1467465,
title = {Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor Agonists as PET Tracers for Pancreatic β cell Imaging},
author = {Bandara, Nilantha and Zheleznyak, Alex and Cherukuri, Kaavya and Griffith, David A. and Limberakis, Chris and Tess, David A. and Jianqing, Chen and Waterhouse, Rikki and Lapi, Suzanne E.},
abstractNote = {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 Cys40exendin-4 (DO3A-VS-Cys40-exendin-4 and NODA-VS-Cys40-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-Cys40-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 [64Cu]DO3A-VS-, 0.14 ± 0.02 %ID/g for [64Cu]NODA-VS-, 0.11 ± 0.03 for [68Ga]DO3A-VS-, and 0.26 ± 0.03 for [68Ga]NODA-VS-Cys40-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: [64Cu]/[68Ga]DO3A-VS-Cys40- and [64Cu]/[68Ga]NODA-VS-Cys40-exendin-4 can be used as PET imaging agents specific for GLP-1R expressed on β cells. Here in this paper, we report the first evidence of pancreatic uptake visualized with exendin-4 derivative in a rat animal model via in vivo dynamic PET imaging.},
doi = {10.1007/s11307-015-0861-5},
journal = {Molecular Imaging and Biology},
number = 1,
volume = 18,
place = {United States},
year = {Tue May 19 00:00:00 EDT 2015},
month = {Tue May 19 00:00:00 EDT 2015}
}
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