title: Highly Increased 125I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst2 Targeting in Human Cancers.
abstract: There is recent in vitro and in vivo evidence that somatostatin receptor subtype 2 (sst2) antagonists are better tools to target neuroendocrine tumors (NETs) than sst2agonists. Indeed, antagonists bind to a greater number of sst2sites than agonists. Whether sst2antagonists could be used successfully to target non-NETs, expressing low sst2density, is unknown. Here, we compare quantitatively125I-JR11 sst2antagonist binding in vitro with that of the sst2agonist125I-Tyr3-octreotide in large varieties of non-NET and NET.
  
  
  
  In vitro receptor autoradiography was performed with125I-JR11 and125I-Tyr3-octreotide in cancers from prostate, breast, colon, kidney, thyroid, and lymphoid tissues as well as NETs as reference.
  
  
  
  In general,125I-JR11 binds to many more sst2sites than125I-Tyr3-octreotide. In 13 breast cancers, 8 had a low binding (mean density, 844 ± 168 dpm/mg of tissue) with the agonist whereas 12 had a high binding (mean density, 4,447 ± 1,128 dpm/mg of tissue) with the antagonist. All 12 renal cell cancers showed a low binding of sst2with the agonist (mean density, 348 ± 49 dpm/mg of tissue) whereas all cases had a high sst2binding with the antagonist (mean density, 3,777 ± 582 dpm/mg of tissue). One of 5 medullary thyroid cancers was positive with the agonist, whereas 5 of 5 were positive with the antagonist. In 15 non-Hodgkin lymphomas, many more sst2sites were labeled with the antagonist than with the agonist. In 14 prostate cancers, none had sst2binding with the agonist and only 4 had a weak binding with the antagonist. None of 17 colon cancers showed sst2sites with the agonist, and only 3 cases were weakly positive with the antagonist. In the various tumor types, adjacent sst2-expressing tissues such as vessels, lymphocytes, nerves, mucosa, or stroma were more strongly labeled with the antagonist than with the agonist. The reference NET cases, incubated with a smaller amount of tracer, were also found to have many more sst2sites measured with the antagonist.
  
  
  
  All renal cell cancers and most breast cancers, non-Hodgkin lymphomas, and medullary thyroid cancers represent novel indications for the in vivo radiopeptide targeting of sst2by sst2antagonists, comparable to NET radiotargeting with sst2agonists.
authors: Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland reubi@pathology.unibe.ch.
authors: Jean Claude
authors: JC
authors: Reubi
authors: Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland.
authors: Beatrice
authors: B
authors: Waser
authors: Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany; and.
authors: Helmut
authors: H
authors: Mäcke
authors: The Salk Institute for Biological Studies, La Jolla, California.
authors: Jean
authors: J
authors: Rivier
mesh_terms: D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D007457:Iodine Radioisotopes; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2
keywords: breast cancer; cancer radiopeptide targeting; renal cell cancer; somatostatin sst2 receptors; sst2 antagonist