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Theranostics 2020; 10(25):11580-11594. doi:10.7150/thno.47485 This issue Cite

Research Paper

A snake toxin as a theranostic agent for the type 2 vasopressin receptor

Laura Droctové1, Manon Lancien1, Vu Long Tran2, Michaël Susset1, Benoit Jego2, Frederic Theodoro3, Pascal Kessler1, Gilles Mourier1, Philippe Robin1, Sékou Siramakan Diarra4, Stefano Palea4, Adrien Flahault5, Amélia Chorfa6, Maithé Corbani6, Catherine Llorens-Cortes7, Bernard Mouillac6, Christiane Mendre6, Alain Pruvost3, Denis Servent1, Charles Truillet2, Nicolas Gilles1✉

1. Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SIMoS, 91191 Gif-sur-Yvette, France.
2. Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, 91401, France.
3. Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, 91191 Gif-sur-Yvette, France.
4. Humana Biosciences, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670, Labège, France.
5. Laboratory of Central Neuropeptides in the Regulation of Body Fluid Homeostasis and Cardiovascular Functions, Center for Interdisciplinary Research in Biology, INSERM, Unit U1050, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7241, Collège de France, Paris, France.
6. IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France.
7. INSERM, Unit U1050, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7241, Collège de France, Paris, France.

✉ Corresponding author: E-mail: nicolas.gillesfr.

Citation:
Droctové L, Lancien M, Tran VL, Susset M, Jego B, Theodoro F, Kessler P, Mourier G, Robin P, Diarra SS, Palea S, Flahault A, Chorfa A, Corbani M, Llorens-Cortes C, Mouillac B, Mendre C, Pruvost A, Servent D, Truillet C, Gilles N. A snake toxin as a theranostic agent for the type 2 vasopressin receptor. Theranostics 2020; 10(25):11580-11594. doi:10.7150/thno.47485. https://www.thno.org/v10p11580.htm
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Abstract

Graphic abstract

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.

Keywords: Snake toxin, cancers, PK/PD, theranostic agent, PET imaging

Citation styles

APA
Droctové, L., Lancien, M., Tran, V.L., Susset, M., Jego, B., Theodoro, F., Kessler, P., Mourier, G., Robin, P., Diarra, S.S., Palea, S., Flahault, A., Chorfa, A., Corbani, M., Llorens-Cortes, C., Mouillac, B., Mendre, C., Pruvost, A., Servent, D., Truillet, C., Gilles, N. (2020). A snake toxin as a theranostic agent for the type 2 vasopressin receptor. Theranostics, 10(25), 11580-11594. https://doi.org/10.7150/thno.47485.

ACS
Droctové, L.; Lancien, M.; Tran, V.L.; Susset, M.; Jego, B.; Theodoro, F.; Kessler, P.; Mourier, G.; Robin, P.; Diarra, S.S.; Palea, S.; Flahault, A.; Chorfa, A.; Corbani, M.; Llorens-Cortes, C.; Mouillac, B.; Mendre, C.; Pruvost, A.; Servent, D.; Truillet, C.; Gilles, N. A snake toxin as a theranostic agent for the type 2 vasopressin receptor. Theranostics 2020, 10 (25), 11580-11594. DOI: 10.7150/thno.47485.

NLM
Droctové L, Lancien M, Tran VL, Susset M, Jego B, Theodoro F, Kessler P, Mourier G, Robin P, Diarra SS, Palea S, Flahault A, Chorfa A, Corbani M, Llorens-Cortes C, Mouillac B, Mendre C, Pruvost A, Servent D, Truillet C, Gilles N. A snake toxin as a theranostic agent for the type 2 vasopressin receptor. Theranostics 2020; 10(25):11580-11594. doi:10.7150/thno.47485. https://www.thno.org/v10p11580.htm

CSE
Droctové L, Lancien M, Tran VL, Susset M, Jego B, Theodoro F, Kessler P, Mourier G, Robin P, Diarra SS, Palea S, Flahault A, Chorfa A, Corbani M, Llorens-Cortes C, Mouillac B, Mendre C, Pruvost A, Servent D, Truillet C, Gilles N. 2020. A snake toxin as a theranostic agent for the type 2 vasopressin receptor. Theranostics. 10(25):11580-11594.

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