Schindler, Lisa and Wohlfahrt, Katrin and von Kruechten, Lara Gluhacevic and Prante, Olaf and Keller, Max and Maschauer, Simone (2022) Neurotensin analogs by fluoroglycosylation at N-omega-carbamoylated arginines for PET imaging of NTS1-positive tumors. SCIENTIFIC REPORTS, 12 (1): 15028. ISSN 2045-2322
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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 Arg(8) or Arg(9) by N-omega-carbamoylation and subsequent fluoroglycosylation provides a suitable approach for the development of NT(8-13) analogs as PET imaging agents. The N-omega-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 [F-18]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, [F-18]21 has the potential to be used as molecular probe for the imaging of NTS1-expressing tumors by PET.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLICK CHEMISTRY; RECEPTOR; PEPTIDES; EXPRESSION; CANCER; BIODISTRIBUTION; GLYCOSYLATION; LIGANDS |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institut für Analytische Chemie, Chemo- und Biosensorik > Instrumentelle Analytik (Prof. Frank-Michael Matysik) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Feb 2024 13:34 |
| Last Modified: | 15 Feb 2024 13:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57691 |
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