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

Bandara, Nilantha; Zheleznyak, Alex; Cherukuri, Kaavya; Griffith, David A.; Limberakis, Chris; Tess, David A.; Jianqing, Chen; Waterhouse, Rikki; Lapi, Suzanne E.

doi:10.1007/s11307-015-0861-5

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

Journal Article · Tue May 19 00:00:00 EDT 2015 · Molecular Imaging and Biology

DOI:https://doi.org/10.1007/s11307-015-0861-5· OSTI ID:1467465

Bandara, Nilantha ^[1]; Zheleznyak, Alex ^[1]; Cherukuri, Kaavya ^[1]; Griffith, David A. ^[2]; Limberakis, Chris ^[3]; Tess, David A. ^[4]; Jianqing, Chen ^[5]; Waterhouse, Rikki ^[5]; Lapi, Suzanne E. ^[1]

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

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-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-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.

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Research Organization:: The Washington Univ., St. Louis, MO (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0002032

OSTI ID:: 1467465

Journal Information:: Molecular Imaging and Biology, Vol. 18, Issue 1; ISSN 1536-1632

Country of Publication:: United States

Language:: English

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Cited by: 10 works

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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

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