title: Stabilization of neurotensin analogues: effect on peptide catabolism, biodistribution and tumor binding.
abstract: Neurotensin (NT) receptors in pancreatic and other neuroendocrine tumors are promising targets for imaging and therapeutic purposes. Here, we report on the effect of distinct changes in the peptide chain on catabolism in vitro for five radiolabeled [99mTc] neurotensin analogues having high affinity for neurotensin receptors. Substitution of NT(1-7) by (NalphaHis)Ac--the Tc-binding moiety--combined with a reduced bond 8-9 (CH2NH), N-methylation of peptide bonds or replacement of Ile(12) by tertiary leucin (Tle) led to peptide stabilization of various degrees. Biodistribution studies in nude mice bearing HT29 xenografts showed higher tumor uptake with more stable peptides, yielding high tumor to blood ratios of up to 70.
authors.affiliation: Paul Scherrer Institute, Center for Radiopharmaceutical Science, CH-5232 PSI, Villigen, Switzerland. peter.blaeuenstein@psi.ch
authors.forename: Matthias
authors.initials: M
authors.lastname: Bruehlmeier
authors.forename: Elisa García
authors.initials: EG
authors.lastname: Garayoa
authors.forename: Alain
authors.initials: A
authors.lastname: Blanc
authors.forename: Barbara
authors.initials: B
authors.lastname: Holzer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gergely
authors.forename: Dirk
authors.initials: D
authors.lastname: Tourwé
authors.forename: Pius August
authors.initials: PA
authors.lastname: Schubiger
authors.forename: Peter
authors.initials: P
authors.lastname: Bläuenstein
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D010455:Peptides; D019275:Radiopharmaceuticals; D009496:Neurotensin