64Cu- and 68Ga-labelled [Nle(14),Lys(40)(Ahx-NODAGA)NH2]-exendin-4 for pancreatic beta cell imaging in rats

K. Mikkola, M. Kirsi, C. Yim, Y. Cheng-Bin, V. Fagerholm, F. Veronica, T. Ishizu, I. Tamiko, V. Elomaa, E. Viki-Veikko, J. Rajander, R. Johan, J. Jurttila, J. Jori, T. Saanijoki, S. Tiina, T. Tolvanen, T. Tuula, M. Tirri, T. Marko, E. Gourni, G. Eleni, M. Béhé, B. Martin, M. Gotthardt, G. Martin, J. Reubi, R. Claude, H. Mäcke, M. Helmut, A. Roivainen, R. Anne, O. Solin, S. Olof, P. Nuutila and N. Pirjo

Turku PET Centre, University of Turku, Turku, Finland.
Apr, 2014

Abstract

Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle(14),Lys(40)(Ahx-NODAGA-(64)Cu)NH2]-exendin-4 ([(64)Cu]NODAGA-exendin-4) and [Nle(14),Lys(40)(Ahx-NODAGA-(68)Ga)NH2]-exendin-4 ([(68)Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents.The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated.We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [(64)Cu]NODAGA-exendin-4 and [(68)Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively.[(64)Cu]NODAGA-exendin-4 might be more effective for labelling islets than [(68)Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [(68)Ga]NODAGA-exendin-4 compared to [(64)Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [(64)Cu]NODAGA-exendin-4 as a clinical tracer.