title: [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.affiliation: Molecular Radiopharmacy, INRASTES, National Center for Scientific Research "Demokritos" , GR-153 10 Athens, Greece.
authors.forename: Theodosia
authors.initials: T
authors.lastname: Maina
authors.forename: Renzo
authors.initials: R
authors.lastname: Cescato
authors.forename: Beatrice
authors.initials: B
authors.lastname: Waser
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Tatsi
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Kaloudi
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: Marion
authors.initials: M
authors.lastname: de Jong
authors.forename: Berthold A
authors.initials: BA
authors.lastname: Nock
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Reubi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D007205:Indium Radioisotopes; D008024:Ligands; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*; D053561:Somatostatin-28 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C000594996:111In-((DOTA)Ser1,Leu8,Trp22,Tyr25)SS28; D007205:Indium Radioisotopes; D008024:Ligands; D009942:Organometallic Compounds; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D053561:Somatostatin-28