Fulltext

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

Antunes, P. ; Ginj, M. ; Zhang, H. ; Waser, B. ; Baum, R. ; Reubi, J. ; Maecke, H.

In: European Journal of Nuclear Medicine and Molecular Imaging, 2007, vol. 34, no. 7, p. 982-993

Aggiungi alla tua lista
    Titre
    • Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?
    Auteur
    • Antunes, P.. Division of Radiological Chemistry, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
    • Ginj, M.. Division of Radiological Chemistry, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
    • Zhang, H.. Division of Radiological Chemistry, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
    • Waser, B.. Institute of Pathology, University of Bern, Bern, Switzerland
    • Baum, R.. Department of Nuclear Medicine/PETCT-Center, Zentralklinik Bad Berka, Bad Berka, Germany
    • Reubi, J.. Institute of Pathology, University of Bern, Bern, Switzerland
    • Maecke, H.. Division of Radiological Chemistry, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • European Journal of Nuclear Medicine and Molecular Imaging, 2007, vol. 34, no. 7, p. 982-993. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:320185
    Summary
    Purpose: Gallium-68 is a metallic positron emitter with a half-life of 68min 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