Design, Synthesis, and Biological Evaluation of the First Radio-Metalated Neurotensin Analogue Targeting Neurotensin Receptor 2
| dc.rights.license | open | en_US |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | BODIN, Sacha | |
| dc.contributor.author | PREVITI, Santo | |
| dc.contributor.author | JESTIN, Emmanuelle | |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | VIMONT, Delphine | |
| dc.contributor.author | AIT-ARSA, Imade | |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | LAMARE, Frederic
ORCID: 0000-0003-1289-7655 | |
| dc.contributor.author | REMOND, Emmanuelle | |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | HINDIE, Elif | |
| dc.contributor.author | CAVELIER, Florine | |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | MORGAT, Clement | |
| dc.date.accessioned | 2023-06-28T07:51:31Z | |
| dc.date.available | 2023-06-28T07:51:31Z | |
| dc.date.issued | 2023-02-21 | |
| dc.identifier.issn | 2470-1343 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/182848 | |
| dc.description.abstractEn | Neurotensin receptor 2 (NTS) is a well-known mediator of central opioid-independent analgesia. Seminal studies have highlighted NTS overexpression in a variety of tumors including prostate cancer, pancreas adenocarcinoma, and breast cancer. Herein, we describe the first radiometalated neurotensin analogue targeting NTS. JMV 7488 (DOTA-(βAla)-Lys-Lys-Pro-(D)Trp-Ile-TMSAla-OH) was prepared using solid-phase peptide synthesis, then purified, radiolabeled with Ga and In, and investigated on HT-29 cells and MCF-7 cells, respectively, and on HT-29 xenografts. [Ga]Ga-JMV 7488 and [In]In-JMV 7488 were quite hydrophilic (logD = -3.1 ± 0.2 and -2.7 ± 0.2, respectively, < 0.0001). Saturation binding studies showed good affinity toward NTS ( = 38 ± 17 nM for [Ga]Ga-JMV 7488 on HT-29 and 36 ± 10 nM on MCF-7 cells; = 36 ± 4 nM for [In]In-JMV 7488 on HT-29 and 46 ± 1 nM on MCF-7 cells) and good selectivity (no NTS binding up to 500 nM). On cell-based evaluation, [Ga]Ga-JMV 7488 and [In]In-JMV 7488 showed high and fast NTS-mediated internalization of 24 ± 5 and 25 ± 11% at 1 h for [In]In-JMV 7488, respectively, along with low NTS-membrane binding (<8%). Efflux was as high as 66 ± 9% at 45 min for [Ga]Ga-JMV 7488 on HT-29 and increased for [In]In-JMV 7488 up to 73 ± 16% on HT-29 and 78 ± 9% on MCF-7 cells at 2 h. Maximum intracellular calcium mobilization of JMV 7488 was 91 ± 11% to that of levocabastine, a known NTS agonist on HT-29 cells demonstrating the agonist behavior of JMV 7488. In nude mice bearing HT-29 xenograft, [Ga]Ga-JMV 7488 showed a moderate but promising significant tumor uptake in biodistribution studies that competes well with other nonmetalated radiotracers targeting NTS. Significant uptake was also depicted in lungs. Interestingly, mice prostate also demonstrated [Ga]Ga-JMV 7488 uptake although the mechanism was not NTS-mediated. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.title.en | Design, Synthesis, and Biological Evaluation of the First Radio-Metalated Neurotensin Analogue Targeting Neurotensin Receptor 2 | |
| dc.title.alternative | ACS Omega | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1021/acsomega.2c07814 | en_US |
| dc.identifier.pubmed | 36844603 | en_US |
| bordeaux.journal | ACS Omega | en_US |
| bordeaux.page | 6994-7004 | en_US |
| bordeaux.volume | 8 | en_US |
| bordeaux.hal.laboratories | Institut de neurosciences cognitives et intégratives d'Aquitaine (INCIA) - UMR 5287 | en_US |
| bordeaux.issue | 7 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.team | Imagerie multimodale translationnelle | |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | pubmed | |
| hal.export | false | |
| workflow.import.source | pubmed | |
| dc.rights.cc | CC BY-NC-ND | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=ACS%20Omega&rft.date=2023-02-21&rft.volume=8&rft.issue=7&rft.spage=6994-7004&rft.epage=6994-7004&rft.eissn=2470-1343&rft.issn=2470-1343&rft.au=BODIN,%20Sacha&PREVITI,%20Santo&JESTIN,%20Emmanuelle&VIMONT,%20Delphine&AIT-ARSA,%20Imade&rft.genre=article |
