Comprehensive evaluation of a somatostatin-based radiolabelled antagonist for diagnostic imaging and radionuclide therapy

Eur J Nucl Med Mol Imaging. 2012 Dec;39(12):1876-85. doi: 10.1007/s00259-012-2231-8. Epub 2012 Aug 29.


Purpose: Targeting of tumours positive for somatostatin receptors (sst) with radiolabelled peptides is of interest for tumour localization, staging, therapy follow-up and targeted radionuclide therapy. The peptides used clinically are exclusively agonists, but recently we have shown that the radiolabelled somatostatin-based antagonist (111)In-DOTA-sst2-ANT may be preferable to agonists. However, a comprehensive study of this radiolabelled antagonist to determine its significance was lacking. The present report describes the evaluation of this novel antagonist labelled with (111)In and (177)Lu in three different tumour models.

Methods: Radiopeptide binding, internalization and dissociation studies were performed using cells expressing HEK293-rsst(2). Biodistribution studies were performed in HEK293-rsst(2), HEK293-hsst(2) and HEK293-rsst(3) xenografted mice.

Results: Saturation binding analysis confirmed earlier IC(50) data for (111/nat)In-DOTA-sst2-ANT and showed similar affinity of (177/nat)Lu-DOTA-sst2-ANT for the sst(2). Only low internalization was found in cell culture (6.68 ± 0.06 % at 4 h), which was not unexpected for an antagonist, and this could be further reduced by the addition of sucrose. No internalization was observed in HEK293 cells not expressing sst. Both results indicate that the internalization was specific. (111)In-DOTA-sst2-ANT and (177)Lu-DOTA-sst2-ANT were shown to target tumour xenografts expressing the rat and the human sst(2) receptor with no differences in their uptake or pharmacokinetics. The uptake in rsst(2) and hsst(2) was high (about 30 %IA/g 4 h after injection) and surprisingly long-lasting (about 20-23 %IA/g 24 h after injection). Kidney uptake was blocked by approximately 50 % by lysine or Gelofusine.

Conclusion: These results indicate that radiolabelled somatostatin-based antagonists may be superior to corresponding agonists. The long tumour retention time of (177)Lu-DOTA-sst2-ANT indicates that this new class of compounds is of relevance not only in diagnostic imaging but also in targeted radionuclide therapy of sst-positive tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • HEK293 Cells
  • Humans
  • Indium Radioisotopes / metabolism
  • Indium Radioisotopes / pharmacokinetics
  • Indium Radioisotopes / therapeutic use
  • Lutetium / metabolism
  • Lutetium / pharmacokinetics
  • Lutetium / therapeutic use
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms / diagnostic imaging
  • Neoplasms / radiotherapy
  • Octreotide / metabolism
  • Octreotide / pharmacokinetics
  • Octreotide / therapeutic use
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Organometallic Compounds / therapeutic use
  • Radionuclide Imaging
  • Radiopharmaceuticals / metabolism
  • Radiopharmaceuticals / pharmacokinetics*
  • Radiopharmaceuticals / therapeutic use
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Receptors, Somatostatin / metabolism
  • Tissue Distribution


  • 111In-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-Phe(4-NO2)-cyclo(Cys-Tyr-Trp-Lys-Thr-Cys)-Tyr-NH2
  • Indium Radioisotopes
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • Lutetium
  • Octreotide