Academic Journal
A snake toxin as a theranostic agent for the type 2 vasopressin receptor
| العنوان: | A snake toxin as a theranostic agent for the type 2 vasopressin receptor |
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| المؤلفون: | Droctové, Laura, Lancien, Manon, Tran, Vu Long, Susset, Michaël, Jego, Benoit, Theodoro, Frederic, Kessler, Pascal, Mourier, Gilles, Robin, Philippe, Diarra, Sékou Siramakan, Palea, Stefano, Flahault, Adrien, Chorfa, Amélia, Corbani, Maithé, Llorens-Cortes, Catherine, Mouillac, Bernard, Mendre, Christiane, Pruvost, Alain, Servent, Denis, Truillet, Charles, Gilles, Nicolas |
| المساهمون: | Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Humana Biosciences, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670, Labège, France., Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris Sciences et Lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Ligue nationale contre le cancer |
| المصدر: | ISSN: 1838-7640 ; Theranostics ; https://hal.science/hal-02960704 ; Theranostics, 2020, 10 (25), pp.11580-11594. ⟨10.7150/thno.47485⟩. |
| بيانات النشر: | HAL CCSD Ivyspring International Publisher |
| سنة النشر: | 2020 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | Snake toxin, cancers, PK/PD, theranostic agent, PET imaging, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology |
| الوصف: | International audience ; Rationale: MQ1, a snake toxin which targets with high nanomolar affinity and absolute selectivity for the type 2 vasopressin receptor (V2R), is a drug candidate for renal diseases and a molecular probe for imaging cells or organs expressing V2R. Methods: MQ1's pharmacological properties were characterized and applied to a rat model of hyponatremia. Its PK/PD parameters were determined as well as its therapeutic index. Fluorescently and radioactively labeled MQ1 were chemically synthesized and associated with moderate loss of affinity. MQ1's dynamic biodistribution was monitored by positron emission tomography. Confocal imaging was used to observe the labeling of three cancer cell lines. Results: The inverse agonist property of MQ1 very efficiently prevented dDAVP-induced hyponatremia in rats with low nanomolar/kg doses and with a very large therapeutic index. PK (plasma MQ1 concentrations) and PD (diuresis) exhibited a parallel biphasic decrease. The dynamic biodistribution showed that MQ1 targets the kidneys and then exhibits a blood and kidney biphasic decrease. Whatever the approach used, we found a T1/2α between 0.9 and 3.8 h and a T1/2β between 25 and 46 h and demonstrated that the kidneys were able to retain MQ1. Finally, the presence of functional V2R expressed at the membrane of cancer cells was, for the first time, demonstrated with a specific fluorescent ligand. Conclusion: As the most selective V2 binder, MQ1 is a new promising drug for aquaresis-related diseases and a molecular probe to visualize in vitro and in vivo V2R expressed physiologically or under pathological conditions. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33052234; hal-02960704; https://hal.science/hal-02960704; https://hal.science/hal-02960704/document; https://hal.science/hal-02960704/file/2020_Droctov%C3%A9_Theranostics.pdf; PUBMED: 33052234; WOS: 000580535400015 |
| DOI: | 10.7150/thno.47485 |
| الاتاحة: | https://hal.science/hal-02960704 https://hal.science/hal-02960704/document https://hal.science/hal-02960704/file/2020_Droctov%C3%A9_Theranostics.pdf https://doi.org/10.7150/thno.47485 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.26A2EEC |
| قاعدة البيانات: | BASE |
| DOI: | 10.7150/thno.47485 |
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