title: [99mTc]Demotensin 5 and 6 in the NTS1-R-targeted imaging of tumours: synthesis and preclinical results.
abstract: OBJECTIVE
  The aim of this study was to evaluate the applicability of [(99m)Tc]Demotensin 5 and 6 [Formula: see text] in the targeted diagnostic imaging of neurotensin subtype 1 receptor (NTS1-R)-expressing tumours.
  
  
  METHODS
  Labelling of Demotensin 5 and 6 with (99m)Tc was conducted by brief incubation with (99m)TcO(4) (-), SnCl(2) and citrate anions in alkaline medium at ambient temperature. Affinities of conjugates for the NTS1-R were determined by competition binding experiments in WiDr cell membranes using [(125)I-Tyr(3)]NT as the radioligand. Saturation binding assays were conducted for [(99m)Tc/(99g)Tc]Demotensin 6 in WiDr cell membranes. Internalisation of [(99m)Tc]Demotensin 5 and 6 was studied at 37 degrees C in WiDr cells. Biodistribution of [(99m)Tc]Demotensin 5 and 6 was performed in female Swiss nu/nu mice bearing human WiDr xenografts.
  
  
  RESULTS
  Unlabelled conjugates showed a high affinity for the human NTS1-R (Demotensin 5 IC(50)=0.03+/-0.01 nM; Demotensin 6 IC(50)=0.08+/-0.02 nM), while high affinity was also exhibited by (radio)metallated [(99m)Tc/(99g)Tc]Demotensin 6 (K (d)=0.13+/-0.01 nM). [(99m)Tc]Demotensin 5 and 6 internalised rapidly and specifically in WiDr cells. After injection in WiDr tumour-bearing mice, radiopeptides, and especially the doubly stabilised [(99m)Tc]Demotensin 6, showed NTS1-R-mediated uptake in the intestines and in the implanted tumour (4.30+/-0.45%ID/g at 1 h post injection) and rapid renal excretion from non-target tissues into the urine.
  
  
  CONCLUSIONS
  [(99m)Tc]Demotensin 6 shows a favourable preclinical profile and further testing in patients is warranted to monitor its eventual applicability as a radiotracer in the diagnostic imaging of NTS1-R-positive tumours.
authors.affiliation: Institute of Radioisotopes - Radiodiagnostic Products, National Center for Scientific Research Demokritos, Ag. Paraskevi Attikis, 153 10 Athens, Greece.
authors.forename: Theodosia
authors.initials: T
authors.lastname: Maina
authors.forename: Anastasia
authors.initials: A
authors.lastname: Nikolopoulou
authors.forename: Eleni
authors.initials: E
authors.lastname: Stathopoulou
authors.forename: Athanassios S
authors.initials: AS
authors.lastname: Galanis
authors.forename: Paul
authors.initials: P
authors.lastname: Cordopatis
authors.forename: Berthold A
authors.initials: BA
authors.lastname: Nock
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009496:Neurotensin / Q000737:chemistry / Q000493:pharmacokinetics*; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D018028:Receptors, Neurotensin / Q000378:metabolism*; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D013667:Technetium