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Development of a Ne...
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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Schindler, L (author)
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Moosbauer, J (author)
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Schmidt, D (author)
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Spruss, T (author)
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Gratz, L (author)
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Ludeke, S (author)
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Hofheinz, F (author)
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Meister, S (author)
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Echtenacher, B (author)
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Bernhardt, G (author)
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Pietzsch, J (author)
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Hellwig, D (author)
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Keller, M (author)
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- 2022-10-08
- 2022
- English.
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:19
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https://doi.org/10.3...
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Abstract
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- 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.
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Cancers
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- By the author/editor
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Schindler, L
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Moosbauer, J
-
Schmidt, D
-
Spruss, T
-
Gratz, L
-
Ludeke, S
-
show more...
-
Hofheinz, F
-
Meister, S
-
Echtenacher, B
-
Bernhardt, G
-
Pietzsch, J
-
Hellwig, D
-
Keller, M
-
show less...
- Articles in the publication
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Cancers
- By the university
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Karolinska Institutet