Development of Radiopharmaceuticals for NPY Receptor-5 (Y5) Nuclear Imaging in Tumors by Synthesis of Specific Agonists and Investigation of Their Binding Mode
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 | PEUKER, Lisa C | |
dc.contributor.author | JESTIN, Emmanuelle | |
hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
dc.contributor.author | ALVES, Isabel D. | |
dc.contributor.author | VELASCO, Valerie | |
dc.contributor.author | AIT-ARSA, Imade | |
hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
dc.contributor.author | SCHOLLHAMMER, Romain | |
hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
dc.contributor.author | LAMARE, Frederic
ORCID: 0000-0003-1289-7655 | |
hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
dc.contributor.author | VIMONT, Delphine | |
dc.contributor.author | MACGROGAN, Gaetan | |
hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
dc.contributor.author | HINDIE, Elif | |
dc.contributor.author | BECK-SICKINGER, Annette G. | |
hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
dc.contributor.author | MORGAT, Clement | |
dc.date.accessioned | 2024-09-02T09:06:53Z | |
dc.date.available | 2024-09-02T09:06:53Z | |
dc.date.issued | 2023-11-15 | |
dc.identifier.issn | 1043-1802 | en_US |
dc.identifier.other | https://pubs.acs.org/doi/10.1021/acs.bioconjchem.3c00313?goto=supporting-info | en_US |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/201373 | |
dc.description.abstractEn | The neuropeptide-Y (NPY) family acts through four G protein-coupled receptor subtypes in humans, namely, Y1, Y2, Y4, and Y5. A growing body of evidence suggest the involvement of the NPY system in several cancers, notably the Y5 subtype, thus acting as a relevant target for the development of radiopharmaceuticals for imaging or targeted radionuclide therapy (TRT). Here, the [cPP(1-7),NPY(19-23),Ala31,Aib32,Gln34]hPP scaffold, further referred to as sY5ago, was modified with a DOTA chelator and radiolabeled with 68Ga and 111In and investigated in vitro and in vivo using the MCF-7 model. For in vivo studies, MCF-7 cells were orthotopically implanted in female nude mice and imaging with small animal positron emission tomography/computed tomography (μPET/CT) was performed. At the end of imaging, the mice were sacrificed. A scrambled version of sY5ago, which was also modified with a DOTA chelator, served as a negative control (DOTA-[Nle]sY5ago_scrambled). sY5ago and DOTA-sY5ago showed subnanomolar affinity toward the Y5 (0.9 ± 0.1 and 0.8 ± 0.1 nM, respectively) and a single binding site at the Y5 was identified. [68Ga]Ga-DOTA-sY5ago and [111In]In-DOTA-sY5ago were hydrophilic and showed high specific internalization (1.61 ± 0.75%/106 cells at 1 h) and moderate efflux (55% of total binding externalized at 45 min). On μPET/CT images, most of the signal was depicted in the kidneys and the liver. MCF-7 tumors were clearly visualized. On biodistribution studies, [68Ga]Ga-DOTA-sY5ago was eliminated by the kidneys (∼60 %ID/g). The kidney uptake is Y5-mediated. A specific uptake was also noted in the liver (5.09 ± 1.15 %ID/g vs 1.13 ± 0.21 %ID/g for [68Ga]Ga-DOTA-[Nle]sY5ago_scrambled, p < 0.05), the lungs (1.03 ± 0.34 %ID/g vs 0.20 %ID/g, p < 0.05), and the spleen (0.85 ± 0.09%ID/g vs 0.16 ± 0.16%ID/g, p < 0.05). In MCF-7 tumors, [68Ga]Ga-DOTA-sY5ago showed 12-fold higher uptake than [68Ga]Ga-DOTA-[Nle]sY5ago_scrambled (3.43 ± 2.32 vs 0.27 ± 0.15 %ID/g, respectively, p = 0.0008) at 1 h post-injection. Finally, a proof-of-principle tissular micro-imaging study on a human primary cancer sample showed weak binding of [111In]In-DOTA-sY5ago in prostatic intra-neoplasia and high binding in the ISUP1 lesion while normal prostate was free of signal. | |
dc.language.iso | EN | en_US |
dc.subject.en | Anatomy | |
dc.subject.en | Biological imaging | |
dc.subject.en | Cancer | |
dc.subject.en | Peptides and proteins | |
dc.subject.en | Rodent models | |
dc.title.en | Development of Radiopharmaceuticals for NPY Receptor-5 (Y5) Nuclear Imaging in Tumors by Synthesis of Specific Agonists and Investigation of Their Binding Mode | |
dc.title.alternative | Bioconjug Chem | en_US |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1021/acs.bioconjchem.3c00313 | en_US |
dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
dc.identifier.pubmed | 37556437 | en_US |
bordeaux.journal | Bioconjugate Chemistry | en_US |
bordeaux.page | 2014-2021 | en_US |
bordeaux.volume | 34 | en_US |
bordeaux.hal.laboratories | Institut de neurosciences cognitives et intégratives d'Aquitaine (INCIA) - UMR 5287 | en_US |
bordeaux.issue | 11 | en_US |
bordeaux.institution | Université de Bordeaux | en_US |
bordeaux.institution | CNRS | en_US |
bordeaux.peerReviewed | oui | en_US |
bordeaux.inpress | non | en_US |
hal.identifier | hal-04683584 | |
hal.version | 1 | |
hal.date.transferred | 2024-09-02T09:06:55Z | |
hal.popular | non | en_US |
hal.audience | Internationale | en_US |
hal.export | true | |
dc.rights.cc | Pas de Licence CC | en_US |
bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Bioconjugate%20Chemistry&rft.date=2023-11-15&rft.volume=34&rft.issue=11&rft.spage=2014-2021&rft.epage=2014-2021&rft.eissn=1043-1802&rft.issn=1043-1802&rft.au=BODIN,%20Sacha&PEUKER,%20Lisa%20C&JESTIN,%20Emmanuelle&ALVES,%20Isabel%20D.&VELASCO,%20Valerie&rft.genre=article |
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