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Title: 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 Cys 40exendin-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 [ 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-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: [ 64Cu]/[ 68Ga]DO3A-VS-Cys 40- and [ 64Cu]/[ 68Ga]NODA-VS-Cys 40-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 amore » rat animal model via in vivo dynamic PET imaging.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [4];  [5];  [5];  [1]
  1. Washington Univ. School of Medicine, St. Louis, MO (United States). Dept. of Radiology
  2. Pfizer Worldwide Research and Development, Cambridge, MA (United States). Worldwide Medicinal Chemistry
  3. Pfizer Worldwide Research and Development, Groton, CT (United States). Worldwide Medicinal Chemistry
  4. Pfizer Worldwide Research and Development, Cambridge, MA (United States). Pharmacokinetics, Dynamics and Metabolism
  5. 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 (Print)
Additional Journal Information:
Journal Name: Molecular Imaging and Biology (Print); 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. 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, 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. doi: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 (Print)},
number = 1,
volume = 18,
place = {United States},
year = {2015},
month = {5}
}

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