Comparison of desferrioxamine and NODAGA for the gallium-68 labeling of exendin-4

• Published in: EJNMMI radiopharmacy and chemistry 2019-05, Vol.4 (1), p.9-9, Article 9
• Main Authors: Kaeppeli, Simon A. M., Schibli, Roger, Mindt, Thomas L., Behe, Martin
• Format: Article
• Language: English
• Subjects: Acids; Butane; Deferoxamine; DFO; Exendin-4; Gallium; GLP-1R; Glucagon; Glucagon-like peptide 1; Hypoglycemia; Imaging; Insulinoma; Kidneys; Labeling; Medicine; Medicine & Public Health; Molecular Medicine; Neuroendocrine tumors; NODAGA; Nuclear Chemistry; Nuclear Medicine; Peptides; Pharmacotherapy; Protein purification; Quality control; Radiology; Research Article; β-cells
• ISSN: 2365-421X; 2365-421X
• DOI: 10.1186/s41181-019-0060-9

Introduction Radiolabeled exendin-4 (Ex4) derivatives are used to target the glucagon-like peptide-1 receptor (GLP-1R) for the clinical diagnosis of insulinomas, a rare type of neuroendocrine tumor. Gallium-68 is an ideal diagnostic nuclide for this application and a study evaluating an exendin-4-NODAGA conjugate is currently underway. However, in complexion with the chelator DFO, its in vivo stability has been a matter of dispute. The aim of this work was to directly compare [ 68 Ga]Ga-Ex4NOD with [ 68 Ga]Ga-Ex4DFO in vitro and in vivo. Methods In our approach, we directly compared N′ -[5-(acetyl-hydroxy-amino)pentyl]- N -[5-[3-(5-aminopentyl-hydroxy-carbamoyl)propanoylamino]pentyl]- N -hydroxy-butane diamide (desferriox-amine B, DFO) and 2-(4,7-bis (carboxymethyl)-1,4,7-triazonan-1-yl) pentanedioic acid (NODAGA) conjugated to exendin-4 in vitro and in vivo . We radiolabeled the peptides with gallium-68, followed by HPLC quality control. In vitro characterization was performed in CHL cells overexpressing the GLP-1R and in vivo studies were conducted with CD1 nu/nu mice carrying tumors derived from these cells. Results We found that both peptides could be radiolabeled with a molar activity of about 9.33 MBq/nmol without further purification. They internalized equally well into GLP-1R-expressing cells and their IC 50 was similar with 15.6 ± 7.8 nM and 18.4 ± 3.0 nM for [ nat Ga]Ga-Ex4NOD and [ nat Ga]Ga-Ex4DFO, respectively. In vivo, [ 68 Ga]Ga-Ex4NOD accumulated more in all tissue, while [ 68 Ga]Ga-Ex4DFO exhibited a more favorable target-to-kidney ratio. Conclusion and relevance DFO is a suitable chelator for the radiolabeling of exendin-4 derivatives with gallium-68 for in vitro and preclinical in vivo studies. DFO performed better in vivo due to its significantly lower kidney accumulation ( p