TY - JOUR
T1 - Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?
AU - Antunes, P.
AU - Ginj, M.
AU - Zhang, H.
AU - Waser, B.
AU - Baum, R. P.
AU - Reubi, J. C.
AU - Maecke, H.
N1 - Funding Information:
Acknowledgements P. Antunes acknowledges the PhD Fellowship of the Fundação para a Ciência e Tecnologia (Ref. SFRH/BD/3136/ 2000). In addition, P. Antunes, M. Ginj, M. Walter and H. Maecke acknowledge the support from the Swiss National Science Foundation project No. 3100A0-100390, BBW project No C00.0091, and the network of excellence, European Molecular Imaging Laboratories (EMIL). The support provided by Novartis Pharma in respect of ESI-MS analysis is gratefully acknowledged. We thank Dr. S. Schulz for the sst3-transfected human embryonic kidney 293 cells. The authors thank K. Hinni and S. Tschumi for biological technical assistance. This work was performed within the COST B12 Action.
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Gallium-68
KW - Imaging
KW - Indium-111
KW - Radiopeptides
KW - Somatostatin receptors
UR - http://www.scopus.com/inward/record.url?scp=34250349188&partnerID=8YFLogxK
U2 - 10.1007/s00259-006-0317-x
DO - 10.1007/s00259-006-0317-x
M3 - Article
C2 - 17225119
AN - SCOPUS:34250349188
VL - 34
SP - 982
EP - 993
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
SN - 1619-7070
IS - 7
ER -