title: Catabolism of neurotensins. Implications for the design of radiolabeling strategies of peptides.
abstract: A major impact in diagnosis and treatment of cancer with peptide based radiopharmaceuticals is expected. Among others neurotensin is considered to be a promising candidate. However, most neurotensin analogues, which bind to the neurotensin receptor have a too short biological half live due to catabolism. Therefore, stabilized fragments have been prepared and labeled with the newly developed [Tc(CO)3](+)-moiety. A single histidine or a (N alpha-His)-Ac group coupled to the N-terminus of the neurotensin fragments were used as a bidentate or a tridentate ligand respectively, which coordinate the metal carbonyl efficiently. Affinity and binding studies of the 99mTc(I) radiolabeled neurotensin fragments revealed a behavior influenced by catabolism and properties of the metal complex.
authors.affiliation: Center for Radiopharmaceutical Science, Swiss Federal Institute of Technology, Zurich.
authors.forename: P A
authors.initials: PA
authors.lastname: Schubiger
authors.forename: L
authors.initials: L
authors.lastname: Allemann-Tannahill
authors.forename: A
authors.initials: A
authors.lastname: Egli
authors.forename: R
authors.initials: R
authors.lastname: Schibli
authors.forename: R
authors.initials: R
authors.lastname: Alberto
authors.forename: N
authors.initials: N
authors.lastname: Carrel-Rémy
authors.forename: M
authors.initials: M
authors.lastname: Willmann
authors.forename: P
authors.initials: P
authors.lastname: Bläuenstein
authors.forename: D
authors.initials: D
authors.lastname: Tourwé
mesh_terms: D000345:Affinity Labels; D001665:Binding Sites; D006207:Half-Life; D006639:Histidine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D009496:Neurotensin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D018028:Receptors, Neurotensin / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D008024:Ligands; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D018028:Receptors, Neurotensin; D009496:Neurotensin; D006639:Histidine