European Journal of Nuclear Medicine and Molecular Imaging

, Volume 34, Issue 7, pp 982–993

Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

Authors

  • P. Antunes
    • Division of Radiological ChemistryUniversity Hospital Basel
  • M. Ginj
    • Division of Radiological ChemistryUniversity Hospital Basel
  • H. Zhang
    • Division of Radiological ChemistryUniversity Hospital Basel
  • B. Waser
    • Institute of PathologyUniversity of Bern
  • R. P. Baum
    • Department of Nuclear Medicine/PETCT-CenterZentralklinik Bad Berka
  • J. C. Reubi
    • Institute of PathologyUniversity of Bern
    • Division of Radiological ChemistryUniversity Hospital Basel
Original Article

DOI: 10.1007/s00259-006-0317-x

Cite this article as:
Antunes, P., Ginj, M., Zhang, H. et al. Eur J Nucl Med Mol Imaging (2007) 34: 982. doi:10.1007/s00259-006-0317-x

Abstract

Purpose

Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [68Ga-DOTA,Tyr3]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its 111In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority.

Methods

Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J.

Results

All peptides showed high affinities on hsst2, with the highest affinity for the GaIII-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the GaIII peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all 67Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the 111In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [67Ga-DOTA,1-Nal3]octreotide in comparison to [111In-DOTA,1-Nal3]octreotide and [67Ga-DOTA,Tyr3]octreotide showed a significantly higher and receptor-mediated uptake of the two 67Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide.

Conclusion

This study demonstrates that 67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies.

Keywords

Somatostatin receptorsGallium-68Indium-111RadiopeptidesImaging

Copyright information

© Springer-Verlag 2007