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

• Published in: Molecular imaging and biology 2016-02, Vol.18 (1), p.90
• Main Authors: Bandara, Nilantha, Zheleznyak, Alex, Cherukuri, Kaavya, Griffith, David A, Limberakis, Chris, Tess, David A, Jianqing, Chen, Waterhouse, Rikki, Lapi, Suzanne E
• Format: Article
• Language: English
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-015-0861-5

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 [beta] cells via targeting of glucagon-like peptide-1 receptor (GLP-1R). Procedures DO3A-VS- and NODA-VS-tagged Cys^sup 40^exendin-4 (DO3A-VS-Cys^sup 40^-exendin-4 and NODA-VS-Cys^sup 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^sup 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 [^sup 64^Cu]DO3A-VS-, 0.14±0.02 %ID/g for [^sup 64^Cu]NODA-VS-, 0.11±0.03 for [^sup 68^Ga]DO3A-VS-, and 0.26±0.03 for [^sup 68^Ga]NODA-VS-Cys^sup 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 [^sup 64^Cu]/[^sup 68^Ga]DO3A-VS-Cys^sup 40^- and [^sup 64^Cu]/[^sup 68^Ga]NODA-VS-Cys^sup 40^-exendin-4 can be used as PET imaging agents specific for GLP-1R expressed on [beta] 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.