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

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

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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Key words

  • Exendin
  • GLP-1R
  • Pancreas
  • Beta cell
  • PET
  • Rat