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Radiolabelling DOTA-peptides with 68Ga

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Abstract

Purpose

A new field of interest is the application of 68Ga-labelled DOTA-conjugated peptides for positron emission tomography (PET). The commercially available or house-made generators require time-consuming and tedious handling of the eluate. Radiolabelling at high specific activities without further purification is not possible, while high specific activities are necessary for peptides that potentially display pharmacological side-effects. Here we present the practical aspects and the results of radiolabelling DOTA-peptides with a TiO2-based commercially available 68Ge/68Ga generator.

Methods

Reaction kinetics and parameters influencing the incorporation of the radionuclide at the highest achievable specific activity were investigated. Since high finger doses were anticipated during handling of the high beta-energy emitter 68Ga, finger dosimetric measurements were performed during radiolabelling and in vivo administration.

Results

Fractionated elution of the generator revealed that 80% of the radioactivity was recovered in 1 ml. Bi- and trivalent ionic contaminants that compete for the incorporation of the radionuclide were below 50 nM; thus further tedious and time-consuming purification was avoided. Radiolabelling was performed at pH 3.5–4. Plastic shielding (≥7-mm wall thickness) around the syringe during administration effectively eliminated the positrons. In rats 68GaCl3 had slow clearance from blood, while 68Ga-EDTA was rapidly cleared via the kidneys. Uptake of 68Ga-DOTATOC in somatostatin receptor-positive tissues was high, with no significant difference between 1 and 4 h post injection.

Conclusion

DOTA-peptides for PET imaging can be labelled with 68Ga up to specific activities of 1 GBq per nmol within 20 min, enabling the clinical application of peptides that display potential pharmacological side-effects.

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Acknowledgements

We thank the working group WG3 from the COST B12 European Community for stimulating discussions. We are grateful to Drs. F. Moet, N. Verstraeten and R. van der Zwart (Mallinckrodt Medical) for the ICP measurements.

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Authors and Affiliations

  1. Erasmus MC Rotterdam, Department of Nuclear Medicine, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands

    Wouter A. P. Breeman, Marion de Jong, Erik de Blois, Bert F. Bernard & Eric P. Krenning

  2. Mallinckrodt Medical, Petten, The Netherlands

    Mark Konijnenberg

Authors
  1. Wouter A. P. Breeman
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  2. Marion de Jong
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  3. Erik de Blois
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  4. Bert F. Bernard
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Corresponding author

Correspondence to Wouter A. P. Breeman.

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Breeman, W.A.P., de Jong, M., de Blois, E. et al. Radiolabelling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging 32, 478–485 (2005). https://doi.org/10.1007/s00259-004-1702-y

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  • DOI: https://doi.org/10.1007/s00259-004-1702-y

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