2. Academic Validation
  3. Neurotensin analogs by fluoroglycosylation at Nω-carbamoylated arginines for PET imaging of NTS1-positive tumors

Neurotensin analogs by fluoroglycosylation at Nω-carbamoylated arginines for PET imaging of NTS1-positive tumors

  • Sci Rep. 2022 Sep 2;12(1):15028. doi: 10.1038/s41598-022-19296-0.
Lisa Schindler 1,  Katrin Wohlfahrt 1 2,  Lara Gluhacevic von Krüchten 1,  Olaf Prante 3,  Max Keller 4,  Simone Maschauer 5
Affiliations

Affiliations

  • 1 Faculty of Chemistry and Pharmacy, Institute of Pharmacy, University of Regensburg, Universitätsstrasse 31, 93053, Regensburg, Germany.
  • 2 Hennig Arzneimittel GmbH & Co KG, Liebigstr. 1-2, 65439, Flörsheim am Main, Germany.
  • 3 Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 12, 91054, Erlangen, Germany.
  • 4 Faculty of Chemistry and Pharmacy, Institute of Pharmacy, University of Regensburg, Universitätsstrasse 31, 93053, Regensburg, Germany. max.keller@chemie.uni-regensburg.de.
  • 5 Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 12, 91054, Erlangen, Germany. simone.maschauer@uk-erlangen.de.
PMID: 36056076 DOI: 10.1038/s41598-022-19296-0
Abstract

Since neurotensin (NT) receptors of subtype-1 (NTS1) are expressed by different types of malignant tumors, such as pancreatic adenocarcinoma, colorectal and prostate carcinoma, they represent an interesting target for tumor imaging by positron emission tomography (PET) and endoradiotherapy. Previously reported neurotensin-derived NTS1 ligands for PET were radiolabeled by modification and prelongation of the N-terminus of NT(8-13) peptide analogs. In this study, we demonstrate that modifying Arg8 or Arg9 by Nω-carbamoylation and subsequent fluoroglycosylation provides a suitable approach for the development of NT(8-13) analogs as PET imaging agents. The Nω-carbamoylated and fluoroglycosylated NT(8-13) analogs retained high NTS1 affinity in the one-digit nanomolar range as well as high metabolic stability in vitro. In vivo, the radioligand [18F]21 demonstrated favorable biokinetics in HT-29 tumor-bearing mice with high tumor uptake and high retention, predominantly renal clearance, and fast wash-out from blood and other non-target tissues. Therefore, [18F]21 has the potential to be used as molecular probe for the imaging of NTS1-expressing tumors by PET.

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