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

• Published in: Molecular imaging and biology Vol. 18; no. 1; pp. 90 - 98
• Main Authors: Bandara, Nilantha, Zheleznyak, Alex, Cherukuri, Kaavya, Griffith, David A., Limberakis, Chris, Tess, David A., Jianqing, Chen, Waterhouse, Rikki, Lapi, Suzanne E.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-02-2016
• Subjects: Animals; Autoradiography; Copper Radioisotopes - metabolism; Cu-64; Exenatide; Exendin-4; Ga-68; Gallium Radioisotopes - metabolism; GLP-1; GLP-1R; Glucagon-Like Peptide-1 Receptor - agonists; Glucagon-Like Peptide-1 Receptor - metabolism; Heterocyclic Compounds, 1-Ring - chemistry; Imaging; Insulin-Secreting Cells - diagnostic imaging; Male; Medicine; Medicine & Public Health; Molecular Imaging - methods; Pancreatic β cells; Peptides - chemistry; PET; Positron-Emission Tomography - methods; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; Radiopharmaceuticals - metabolism; Rats, Sprague-Dawley; Research Article; Signal Processing, Computer-Assisted; Tissue Distribution; Tomography, X-Ray Computed; Venoms - chemistry; Vinyl Compounds - chemistry; β cell mass; Ga-68; GLP-1; Pancreatic β cells; β cell mass; PET; GLP-1R; Exendin-4; Cu-64
• 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 β cells via targeting of glucagon-like peptide-1 receptor (GLP-1R).
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.
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.
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.