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Schindler, Lisa Verena [VerfasserIn]; Moosbauer, Jutta [VerfasserIn]; Schmidt, Daniel [VerfasserIn]; Spruss, Thilo [VerfasserIn]; Grätz, Lukas [VerfasserIn]; Lüdeke, Steffen [VerfasserIn]; Hofheinz, Frank [VerfasserIn]; Meister, Sebastian [VerfasserIn]; Echtenacher, Bernd [VerfasserIn]; Bernhardt, Günther [VerfasserIn]; Pietzsch, Jens [VerfasserIn]; Hellwig, Dirk [VerfasserIn]; Keller, Max [VerfasserIn]

Development of a neurotensin-derived 68Ga-labeled PET ligand with high in vivo stability for imaging of NTS1 receptor-expressing tumors

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  • Medientyp: E-Artikel
  • Titel: Development of a neurotensin-derived 68Ga-labeled PET ligand with high in vivo stability for imaging of NTS1 receptor-expressing tumors
  • Beteiligte: Schindler, Lisa Verena [VerfasserIn]; Moosbauer, Jutta [VerfasserIn]; Schmidt, Daniel [VerfasserIn]; Spruss, Thilo [VerfasserIn]; Grätz, Lukas [VerfasserIn]; Lüdeke, Steffen [VerfasserIn]; Hofheinz, Frank [VerfasserIn]; Meister, Sebastian [VerfasserIn]; Echtenacher, Bernd [VerfasserIn]; Bernhardt, Günther [VerfasserIn]; Pietzsch, Jens [VerfasserIn]; Hellwig, Dirk [VerfasserIn]; Keller, Max [VerfasserIn]
  • Erschienen: Freiburg: Universität, 2022
  • Erschienen in: Cancers ; 14(2022), 19, Artikel-ID 4922, Seite 1-30
  • Sprache: Englisch
  • DOI: 10.3390/cancers14194922
  • ISSN: 2072-6694
  • Identifikator:
  • Entstehung:
  • Anmerkungen: Cancers. - 14, 19 (2022) , 4922, ISSN: 2072-6694
  • Beschreibung: Abstract: Overexpression of the neurotensin receptor type 1 (NTS1R), a peptide receptor located at the plasma membrane, has been reported for a variety of malignant tumors. Thus, targeting the NTS1R with 18F- or 68Ga-labeled ligands is considered a straightforward approach towards in vivo imaging of NTS1R-expressing tumors via positron emission tomography (PET). The development of suitable peptidic NTS1R PET ligands derived from neurotensin is challenging due to proteolytic degradation. In this study, we prepared a series of NTS1R PET ligands based on the C-terminal fragment of neurotensin (NT(8–13), Arg8-Arg9-Pro10-Tyr11-Ile12-Leu13) by attachment of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an Nω-carbamoylated arginine side chain. Insertion of Ga3+ in the DOTA chelator gave potential PET ligands that were evaluated concerning NTS1R affinity (range of Ki values: 1.2–21 nM) and plasma stability. Four candidates were labeled with 68Ga3+ and used for biodistribution studies in HT-29 tumor-bearing mice. [68Ga]UR-LS130 ([68Ga]56), containing an N-terminal methyl group and a β,β-dimethylated tyrosine instead of Tyr11, showed the highest in vivo stability and afforded a tumor-to-muscle ratio of 16 at 45 min p.i. Likewise, dynamic PET scans enabled a clear tumor visualization. The accumulation of [68Ga]56 in the tumor was NTS1R-mediated, as proven by blocking studies
  • Zugangsstatus: Freier Zugang