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64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats

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An Erratum to this article was published on 14 November 2013

Abstract

Purpose

Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle14,Lys40(Ahx-NODAGA-64Cu)NH2]-exendin-4 ([64Cu]NODAGA-exendin-4) and [Nle14,Lys40(Ahx-NODAGA-68Ga)NH2]-exendin-4 ([68Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents.

Procedures

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.

Results

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 [64Cu]NODAGA-exendin-4 and [68Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively.

Conclusion

[64Cu]NODAGA-exendin-4 might be more effective for labelling islets than [68Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [68Ga]NODAGA-exendin-4 compared to [64Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [64Cu]NODAGA-exendin-4 as a clinical tracer.

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Acknowledgments

The authors thank Dr. Jörn Schlesinger for technical expertise and scientific discussions and Vesa Oikonen MSc for helping with PET/CT data analysis. Aake Honkaniemi, Elisa Riuttala, Merja Tuomas and Marko Vehmanen are acknowledged for their technical assistance. The study was conducted within the Finnish Centre of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research, financially supported by the Academy of Finland, the University of Turku, Turku University Hospital and Åbo Akademi University. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement 222980 and from the Diabetes Research Foundation, Finland.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Turku PET Centre, University of Turku, Turku, Finland

    Mikkola Kirsi, Yim Cheng-Bin, Fagerholm Veronica, Ishizu Tamiko, Elomaa Viki-Veikko, Jurttila Jori, Saanijoki Tiina, Tolvanen Tuula, Tirri Marko, Roivainen Anne, Solin Olof & Nuutila Pirjo

  2. Accelerator Laboratory, Åbo Akademi University, Turku, Finland

    Rajander Johan & Solin Olof

  3. Turku Center for Disease Modeling, University of Turku, Turku, Finland

    Tirri Marko & Roivainen Anne

  4. Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany

    Gourni Eleni & Mäcke Helmut

  5. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Viiligen-PSI, Switzerland

    Béhé Martin

  6. Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Gotthardt Martin

  7. Division of Cell Biology and Exp. Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland

    Reubi Jean Claude

  8. Department of Endocrinology, Turku University Hospital, Turku, Finland

    Nuutila Pirjo

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  1. Mikkola Kirsi
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Corresponding author

Correspondence to Nuutila Pirjo.

Additional information

Mikkola Kirsi and Yim Cheng-Bin contributed equally to this work.

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Kirsi, M., Cheng-Bin, Y., Veronica, F. et al. 64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats. Mol Imaging Biol 16, 255–263 (2014). https://doi.org/10.1007/s11307-013-0691-2

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