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

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 18F-labeled radioligand for imaging NTS2 expression in vivo by positron emission tomography (PET). The radiosynthesis of glycopeptoid 18F-4 was realized by copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC), applying the prosthetic group 6-deoxy-6-[18F]fluoroglucosyl azide for 18F-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 7 nM with excellent subtype selectivity over NTS1 (260-fold). In vitro autoradiography studies of rat brain slices confirmed the high selectivity of 18F-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 18F-4 in NTS2-positive tumors. As 18F-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.

Figure optionsDownload as PowerPoint slide