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

  • Xuejuan Wang
  • Melpomeni Fani
  • Stefan Schulz
  • Jean Rivier
  • Jean Claude Reubi
  • Helmut R. MaeckeEmail author
Original Article



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 111In-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 111In and 177Lu in three different tumour models.


Radiopeptide binding, internalization and dissociation studies were performed using cells expressing HEK293-rsst2. Biodistribution studies were performed in HEK293-rsst2, HEK293-hsst2 and HEK293-rsst3 xenografted mice.


Saturation binding analysis confirmed earlier IC50 data for 111/natIn-DOTA-sst2-ANT and showed similar affinity of 177/natLu-DOTA-sst2-ANT for the sst2. 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. 111In-DOTA-sst2-ANT and 177Lu-DOTA-sst2-ANT were shown to target tumour xenografts expressing the rat and the human sst2 receptor with no differences in their uptake or pharmacokinetics. The uptake in rsst2 and hsst2 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.


These results indicate that radiolabelled somatostatin-based antagonists may be superior to corresponding agonists. The long tumour retention time of 177Lu-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.


Somatostatin Antagonist Imaging Radionuclide therapy 



Human embryonic kidney


1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid




Dulbecco’s modified Eagle’s medium


Bovine serum albumin


Fetal bovine serum


Phosphate-buffered saline


2-[4-(2-Hydroxyethyl)piperazin-1-yl]ethanesulphonic acid



We thank the Swiss National Science Foundation and the FP7 project TARCC for financial support, and also the COST action D38.

Conflicts of interest



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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Xuejuan Wang
    • 1
  • Melpomeni Fani
    • 1
  • Stefan Schulz
    • 2
  • Jean Rivier
    • 3
  • Jean Claude Reubi
    • 4
  • Helmut R. Maecke
    • 1
    • 5
    Email author
  1. 1.Division of Radiological ChemistryUniversity Hospital BaselBaselSwitzerland
  2. 2.Department of Pharmacology and ToxicologyJena University Hospital - Friedrich Schiller University JenaJenaGermany
  3. 3.The Clayton Foundation Laboratories for Peptide BiologyThe Salk Institute for Biological StudiesLa JollaUSA
  4. 4.Division of Cell Biology and Experimental Cancer Research, Institute of PathologyUniversity of BernBernSwitzerland
  5. 5.Department of Nuclear MedicineUniversity Hospital FreiburgFreiburgGermany

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