18F- and 68Ga-Labeled Neurotensin Peptides for PET Imaging of Neurotensin Receptor 1

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• 作者：Simone Maschauer ; Jürgen Einsiedel ; Harald Hübner ; Peter Gmeiner ; Olaf Prante
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：July 14, 2016
• 年：2016
• 卷：59
• 期：13
• 页码：6480-6492
• 全文大小：584K
• 年卷期：0
• ISSN：1520-4804

文摘

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 ⁶⁸Ga-labeling or propargylglycine for ¹⁸F-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 [⁶⁸Ga]6 and [⁶⁸Ga]8 and specific binding in small-animal PET studies. The tumor uptake of ⁶⁸Ga-labeled peptides in vivo significantly correlated with the in vitro K_i values for NTS1. [⁶⁸Ga]8 displayed an excellent tumor-to-background ratio and could therefore be considered as an appropriate molecular probe for NTS1 imaging by PET.