[111In-DOTA]LTT-SS28, a first pansomatostatin radioligand for in vivo targeting of somatostatin receptor-positive tumors.

Abstract

Radiolabeled pansomatostatin-like analogues are expected to enhance the diagnostic sensitivity and to expand the clinical indications of currently applied sst2-specific radioligands. In this study, we present the somatostatin mimic [DOTA]LTT-SS28 {[(DOTA)Ser1,Leu8,D-Trp22,Tyr25]SS28} and its 111In radioligand. [DOTA]LTT-SS28 exhibited a pansomatostatin-like profile binding with high affinity to all five hsst1-hsst5 subtypes (IC50 values in the lower nanomolar range). Furthermore, [DOTA]LTT-SS28 behaved as an agonist at hsst2, hsst3, and hsst5, efficiently stimulating internalization of the three receptor subtypes. Radioligand [111In-DOTA]LTT-SS28 showed good stability in the mouse bloodstream. It displayed strong and specific uptake in AR42J tumors 4 h postinjection (9.3±1.6% ID/g vs 0.3±0.0% ID/g during sst2 blockade) in mice. Significant and specific uptake was also observed in HEK293-hsst2-, HEK293-hsst3-, and HEK293-hsst5-expressing tumors (4.43±1.5, 4.88±1.1, and <3% ID/g, respectively, with values of <0.5% ID/g during receptor blockade). In conclusion, the somatostatin mimic [111In-DOTA]LTT-SS28 specifically localizes in sst2-, sst3-, and sst5-expressing xenografts in mice showing promise for multi-sst1-sst5 targeted tumor imaging.

• Authors: Theodosia Maina, Renzo Cescato, Beatrice Waser, Aikaterini Tatsi, Aikaterini Kaloudi, Eric P Krenning, Marion de Jong, Berthold A Nock, Jean Claude Reubi
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 57 Issue 15 Pg. 6564-71 (Aug 14 2014) ISSN: 1520-4804 [Electronic] United States
• PMID: 25007399 (Publication Type: Journal Article)

Chemical References

• 111In-((DOTA)Ser1,Leu8,Trp22,Tyr25)SS28
• Indium Radioisotopes
• Ligands
• Organometallic Compounds
• Peptide Fragments
• Radiopharmaceuticals
• Receptors, Somatostatin
• Somatostatin-28

Topics

• Animals
• Cell Line, Tumor
• HEK293 Cells
• Heterografts
• Humans
• Indium Radioisotopes
• Ligands
• Mice, SCID
• Neoplasm Transplantation
• Organometallic Compounds (chemical synthesis, chemistry, pharmacokinetics)
• Peptide Fragments (chemical synthesis, chemistry, pharmacokinetics)
• Radioligand Assay
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
• Receptors, Somatostatin (agonists, metabolism)
• Somatostatin-28 (analogs & derivatives, chemical synthesis, chemistry, pharmacokinetics)
• Tissue Distribution