title: (18)F- and (68)Ga-Labeled Neurotensin Peptides for PET Imaging of Neurotensin Receptor 1.
abstract: The neurotensin (NT) receptor-1 (NTS1) is overexpressed in a variety of carcinomas and is therefore an interesting target for imaging with positron emission tomography (PET). The aim of this study was the development of new NT derivatives based on the metabolically stable peptide sequence NLys-Lys-Pro-Tyr-Tle-Leu suitable for PET imaging. The NT peptides were synthesized by solid-phase supported peptide synthesis and elongated with respective chelators (NODA-GA, DOTA) for (68)Ga-labeling or propargylglycine for (18)F-labeling via copper-catalyzed azide-alkyne cycloaddition. Receptor affinities of the peptides for NTS1 were in the range of 19-110 nM. Biodistribution studies using HT29 tumor-bearing mice showed highest tumor uptake for [(68)Ga]6 and [(68)Ga]8 and specific binding in small-animal PET studies. The tumor uptake of (68)Ga-labeled peptides in vivo significantly correlated with the in vitro Ki values for NTS1. [(68)Ga]8 displayed an excellent tumor-to-background ratio and could therefore be considered as an appropriate molecular probe for NTS1 imaging by PET.
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich-Alexander University (FAU) , Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Maschauer
authors.affiliation: Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University (FAU) , Schuhstraße 19, 91052 Erlangen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Einsiedel
authors.affiliation: Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University (FAU) , Schuhstraße 19, 91052 Erlangen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Hübner
authors.affiliation: Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University (FAU) , Schuhstraße 19, 91052 Erlangen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Gmeiner
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich-Alexander University (FAU) , Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Prante
mesh_terms: D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D009496:Neurotensin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography; D018028:Receptors, Neurotensin / Q000032:analysis* / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin