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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
- Article/chapterEnglish2022
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:150875956
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http://kipublications.ki.se/Default.aspx?queryparsed=id:150875956URI
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https://doi.org/10.3390/cancers14194922DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
Added entries (persons, corporate bodies, meetings, titles ...)
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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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In:Cancers: MDPI AG14:192072-6694
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Cancers
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Schindler, L
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Moosbauer, J
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Schmidt, D
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Spruss, T
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Gratz, L
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Ludeke, S
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Hofheinz, F
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Meister, S
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Echtenacher, B
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Bernhardt, G
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Pietzsch, J
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Hellwig, D
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Keller, M
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- Articles in the publication
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Cancers
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Karolinska Institutet