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

A1 Refereed original research article in a scientific journal

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

Subtitle: Imaging Beta Cells with 64Cu- and 68Ga-Labelled NODAGA-Exendin-4

Authors: Mikkola Kirsi, Yim Cheng-Bin, Fagerholm Veronica, Ishizu Tamiko, Elomaa Viki-Veikko, Rajander Johan, Jurttila Jori, Saanijoki Tiina, Tolvanen Tuula, Tirri Marko, Gourni Eleni, Béhé Martin, Gotthardt Martin, Reubi Jean Claude, Mäcke Helmut, Roivainen Anne, Solin Olof, Nuutila Pirjo

Publication year: 2014

Journal: Molecular Imaging and Biology

Journal acronym: MIB

Volume: 16

Issue: 2

First page : 255

Last page: 263

Number of pages: 9

ISSN: 1536-1632

eISSN: 1860-2002

DOI: https://doi.org/10.1007/s11307-013-0691-2

Web address : http://link.springer.com/article/10.1007/s11307-013-0691-2

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.