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Bioorg Med Chem. 2015 Jul 15;23(14):4026-33. doi: 10.1016/j.bmc.2015.01.053. Epub 2015 Feb 7.

Improved radiosynthesis and preliminary in vivo evaluation of a (18)F-labeled glycopeptide-peptoid hybrid for PET imaging of neurotensin receptor 2.

Author information

1
Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany.
2
Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University Erlangen-Nürnberg (FAU), Schuhstraße 19, 91052 Erlangen, Germany.
3
Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany. Electronic address: olaf.prante@uk-erlangen.de.

Abstract

The neurotensin receptor 2 (NTS2) is an attractive target for cancer imaging, as it is overexpressed in a variety of tumor types including prostate, pancreas and breast carcinoma. The aim of this study was the development of the first NTS2 subtype selective (18)F-labeled radioligand for imaging NTS2 expression in vivo by positron emission tomography (PET). The radiosynthesis of glycopeptoid (18)F-4 was realized by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), applying the prosthetic group 6-deoxy-6-[(18)F]fluoroglucosyl azide for (18)F-fluoroglycosylation of the alkyne-terminated NT(8-13) analog Pra-N-Me-Arg-Arg-Pro-N-homo-Tyr-Ile-Leu-OH. The binding affinity of the peptide-peptoid 4 for NTS2 was 7nM with excellent subtype selectivity over NTS1 (260-fold). In vitro autoradiography studies of rat brain slices confirmed the high selectivity of (18)F-4 for NTS2. Biodistribution experiments using HT29 and PC3 tumor-bearing nude mice revealed high renal and only moderate tumor uptake, while PET imaging experiments revealed specific binding of (18)F-4 in NTS2-positive tumors. As (18)F-4 displayed high stability in vitro but fast degradation in vivo, future work will focus on the development of metabolically more stable NT(8-13) analogs.

KEYWORDS:

Cancer imaging; Fluorine-18; Neurotensin; Neurotensin receptor 2; PET; Peptoid; Positron emission tomography

PMID:
25691211
DOI:
10.1016/j.bmc.2015.01.053
[Indexed for MEDLINE]

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