Brain-targeting by optimized 99mTc-olanzapine: in vivo and in silico studies

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dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorIbrahim, A.B.
dc.contributor.authorShamsel-Din, H.A
dc.contributor.authorHussein, A.S
dc.contributor.authorSalem, M.A
dc.date.accessioned2020-05-30T12:27:07Z
dc.date.available2020-05-30T12:27:07Z
dc.date.issued2020-05
dc.descriptionScopusen_US
dc.description.abstractPurpose: Olanzapine (OLZ) is an atypical antipsychotic agent that is characterized by low brain porousness. The present work aimed to develop radiolabeled olanzapine (OLZ) without colloidal impurities and evaluate its biodistribution following intravenous (I.V.) and intranasal (I.N.) administration as a potential agent for brain diagnosis. Materials and methods: OLZ was radiolabeled with technetium-99m by using sodium dithionite as the reducing agent. Biodistribution of 99mTc-OLZ complex in mice following I.V. and I.N. administrations was examined. Furthermore, a molecular docking study was performed.Results: Sodium dithionite labeling procedure resulted in highest radiochemical yield (96.30 ± 0.09%) and in vitro stability in serum up to 8 h. Biodistribution study of 99mTc-OLZ complex showed high brain uptake following I.N. (6.2 ± 0.12% ID/g) and I.V. (5.5 ± 0.09% ID/g) at 0.5 and 1 h post administration (P.I.), respectively. Docking into two brain targets predicts higher affinity of 99mTc-OLZ than free OLZ. Additionally, docking to P-glycoproteins shows less affinity for the radiolabelled OLZ and hence it is expected to be associated with better brain exposure than free OLZ.Conclusion: These chemical and preliminary biological merits strongly suggest that the 99mTc-OLZ complex with new reducing agent could be used as a potential diagnostic agent for brain.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=29904&tip=sid&clean=0
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dc.identifier.doihttps://doi.org/10.1080/09553002.2020.1761568
dc.identifier.issn9553002
dc.identifier.otherhttps://doi.org/10.1080/09553002.2020.1761568
dc.identifier.urihttps://t.ly/Z4Mr
dc.identifier.urihttps://t.ly/QHr5
dc.language.isoen_USen_US
dc.publisherTaylor and Francis Ltden_US
dc.relation.ispartofseriesInternational Journal of Radiation Biology;
dc.subjectOlanzapineen_US
dc.subjectbrain diagnosisen_US
dc.subjectdockingen_US
dc.subjectsodium dithioniteen_US
dc.subjecttechnetium-99m.en_US
dc.titleBrain-targeting by optimized 99mTc-olanzapine: in vivo and in silico studiesen_US
dc.typeArticleen_US

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