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Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis

dc.rights.licenseopenen_US
dc.contributor.authorLOUIS, Beatrice
dc.contributor.authorNAIL, Vincent
dc.contributor.authorNACHAR, Oriane
dc.contributor.authorBOUHLEL, Ahlem
dc.contributor.authorMOYON, Anais
dc.contributor.authorBALASSE, Laure
dc.contributor.authorSIMONCINI, Stephanie
dc.contributor.authorCHABERT, Adrien
dc.contributor.authorFERNANDEZ, Samantha
dc.contributor.authorBRIGE, Pauline
dc.contributor.authorHACHE, Guillaume
dc.contributor.authorTINTARU, Aura
hal.structure.identifierInstitut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA]
dc.contributor.authorMORGAT, Clement
dc.contributor.authorDIGNAT-GEORGE, Francoise
dc.contributor.authorGARRIGUE, Philippe
dc.contributor.authorGUILLET, Benjamin
dc.date.accessioned2023-06-28T08:01:36Z
dc.date.available2023-06-28T08:01:36Z
dc.date.issued2023-03-27
dc.identifier.issn1573-7209en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182849
dc.description.abstractEnAPJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [Ga]Ga-AP747 and [Ga]Ga-RGD small animal PET/CT. [Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [Ga]Ga-RGD. Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [Ga]Ga-AP747 PET signal was more than twice higher than that of [Ga]Ga-RGD on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [Ga]Ga-RGD.
dc.description.sponsorshipFrance Life Imagingen_US
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enAngiogenesis
dc.subject.enApelin
dc.subject.enAPJ
dc.subject.enPET imaging
dc.subject.enTheranostics
dc.title.enDesign and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis
dc.title.alternativeAngiogenesisen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1007/s10456-023-09875-8en_US
dc.identifier.pubmed36973482en_US
bordeaux.journalAngiogenesisen_US
bordeaux.hal.laboratoriesInstitut de neurosciences cognitives et intégratives d'Aquitaine (INCIA) - UMR 5287en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.teamImagerie multimodale translationnelle
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
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dc.rights.ccCC BY-NC-NDen_US
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