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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.licenseopenen_US
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorBODIN, Sacha
dc.contributor.authorPEUKER, Lisa C
dc.contributor.authorJESTIN, Emmanuelle
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorALVES, Isabel D.
dc.contributor.authorVELASCO, Valerie
dc.contributor.authorAIT-ARSA, Imade
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorSCHOLLHAMMER, Romain
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorLAMARE, Frederic
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorVIMONT, Delphine
dc.contributor.authorMACGROGAN, Gaetan
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorHINDIE, Elif
dc.contributor.authorBECK-SICKINGER, Annette G.
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorMORGAT, Clement
dc.date.accessioned2024-09-02T09:06:53Z
dc.date.available2024-09-02T09:06:53Z
dc.date.issued2023-11-15
dc.identifier.issn1043-1802en_US
dc.identifier.otherhttps://pubs.acs.org/doi/10.1021/acs.bioconjchem.3c00313?goto=supporting-infoen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/201373
dc.description.abstractEnThe 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.isoENen_US
dc.subject.enAnatomy
dc.subject.enBiological imaging
dc.subject.enCancer
dc.subject.enPeptides and proteins
dc.subject.enRodent models
dc.title.enDevelopment of Radiopharmaceuticals for NPY Receptor-5 (Y5) Nuclear Imaging in Tumors by Synthesis of Specific Agonists and Investigation of Their Binding Mode
dc.title.alternativeBioconjug Chemen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1021/acs.bioconjchem.3c00313en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed37556437en_US
bordeaux.journalBioconjugate Chemistryen_US
bordeaux.page2014-2021en_US
bordeaux.volume34en_US
bordeaux.hal.laboratoriesInstitut de neurosciences cognitives et intégratives d'Aquitaine (INCIA) - UMR 5287en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04683584
hal.version1
hal.date.transferred2024-09-02T09:06:55Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Bioconjugate%20Chemistry&amp;rft.date=2023-11-15&amp;rft.volume=34&amp;rft.issue=11&amp;rft.spage=2014-2021&amp;rft.epage=2014-2021&amp;rft.eissn=1043-1802&amp;rft.issn=1043-1802&amp;rft.au=BODIN,%20Sacha&amp;PEUKER,%20Lisa%20C&amp;JESTIN,%20Emmanuelle&amp;ALVES,%20Isabel%20D.&amp;VELASCO,%20Valerie&amp;rft.genre=article


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