Synthesis and evaluation of [18F]FEtLos and [18F]AMBF3Los as novel 18F-labelled losartan derivatives for molecular imaging of angiotensin II type 1 receptors

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dc.contributor.authorPIJEIRA, MARTHA S.O.pt_BR
dc.contributor.authorNUNES, PAULO S.G.pt_BR
dc.contributor.authorSANTOS, SOFIA N. dospt_BR
dc.contributor.authorZHANG, ZHENGXINGpt_BR
dc.contributor.authorNARIO, ARIAN P.pt_BR
dc.contributor.authorPERINI, EFRAIN A.pt_BR
dc.contributor.authorTURATO, WALTER M.pt_BR
dc.contributor.authorRIERA, ZALUA R.pt_BR
dc.contributor.authorCHAMMAS, ROGERpt_BR
dc.contributor.authorELSINGA, PHILIP H.pt_BR
dc.contributor.authorLIN, KUO-SHYANpt_BR
dc.contributor.authorCARVALHO, IVONEpt_BR
dc.contributor.authorBERNARDES, EMERSON S.pt_BR
dc.coverageInternacionalpt_BR
dc.date.accessioned2020-09-30T17:57:14Z
dc.date.available2020-09-30T17:57:14Z
dc.date.issued2020pt_BR
dc.description.abstractLosartan is widely used in clinics to treat cardiovascular related diseases by selectively blocking the angiotensin II type 1 receptors (AT1Rs), which regulate the renin-angiotensin system (RAS). Therefore, monitoring the physiological and pathological biodistribution of AT1R using positron emission tomography (PET) might be a valuable tool to assess the functionality of RAS. Herein, we describe the synthesis and characterization of two novel losartan derivatives PET tracers, [18F]fluoroethyl-losartan ([18F]FEtLos) and [18F]ammoniomethyltrifluoroborate-losartan ([18F]AMBF3Los). [18F]FEtLos was radiolabeled by 18F-fluoroalkylation of losartan potassium using the prosthetic group 2-[18F]fluoroethyl tosylate; whereas [18F]AMBF3Los was prepared following an one-step 18F-19F isotopic exchange reaction, in an overall yield of 2.7 ± 0.9% and 11 ± 4%, respectively, with high radiochemical purity (>95%). Binding competition assays in AT1R-expressing membranes showed that AMBF3Los presented an almost equivalent binding affinity (Ki 7.9 nM) as the cold reference Losartan (Ki 1.5 nM), unlike FEtLos (Ki 2000 nM). In vitro and in vivo assays showed that [18F]AMBF3Los displayed a good binding affinity for AT1R-overexpressing CHO cells and was able to specifically bind to renal AT1R. Hence, our data demonstrate [18F]AMBF3Los as a new tool for PET imaging of AT1R with possible applications for the diagnosis of cardiovascular, inflammatory and cancer diseases.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorshipIDFAPESP: 12/06875-6pt_BR
dc.description.sponsorshipIDCAPES: 001pt_BR
dc.format.extent1-21pt_BR
dc.identifier.citationPIJEIRA, MARTHA S.O.; NUNES, PAULO S.G.; SANTOS, SOFIA N. dos; ZHANG, ZHENGXING; NARIO, ARIAN P.; PERINI, EFRAIN A.; TURATO, WALTER M.; RIERA, ZALUA R.; CHAMMAS, ROGER; ELSINGA, PHILIP H.; LIN, KUO-SHYAN; CARVALHO, IVONE; BERNARDES, EMERSON S. Synthesis and evaluation of [18F]FEtLos and [18F]AMBF3Los as novel 18F-labelled losartan derivatives for molecular imaging of angiotensin II type 1 receptors. <b>Molecules</b>, v. 25, n. 8, p. 1-21, 2020. DOI: <a href="https://dx.doi.org/10.3390/molecules25081872">10.3390/molecules25081872</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/31407.
dc.identifier.doi10.3390/molecules25081872pt_BR
dc.identifier.fasciculo8pt_BR
dc.identifier.issn1420-3049pt_BR
dc.identifier.orcid0000-0002-0029-7313pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-0029-7313
dc.identifier.percentilfi63.00pt_BR
dc.identifier.percentilfiCiteScore62.57
dc.identifier.urihttp://repositorio.ipen.br/handle/123456789/31407
dc.identifier.vol25pt_BR
dc.relation.ispartofMoleculespt_BR
dc.rightsopenAccesspt_BR
dc.subjectdrugs
dc.subjectcardiovascular diseases
dc.subjectangiotensin
dc.subjectin vitro
dc.subjectpositron computed tomography
dc.subjectautoradiography
dc.titleSynthesis and evaluation of [18F]FEtLos and [18F]AMBF3Los as novel 18F-labelled losartan derivatives for molecular imaging of angiotensin II type 1 receptorspt_BR
dc.typeArtigo de periódicopt_BR
dspace.entity.typePublication
ipen.autorSOFIA NASCIMENTO DOS SANTOS
ipen.autorEFRAIN ARAUJO PERINI
ipen.autorEMERSON SOARES BERNARDES
ipen.autorARIAN PEREZ NARIO
ipen.autorMARTHA SAHYLI ORTEGA PIJIEIRA
ipen.codigoautor14464
ipen.codigoautor9691
ipen.codigoautor12099
ipen.codigoautor14076
ipen.codigoautor14075
ipen.contributor.ipenauthorSOFIA NASCIMENTO DOS SANTOS
ipen.contributor.ipenauthorEFRAIN ARAUJO PERINI
ipen.contributor.ipenauthorEMERSON SOARES BERNARDES
ipen.contributor.ipenauthorARIAN PEREZ NARIO
ipen.contributor.ipenauthorMARTHA SAHYLI ORTEGA PIJIEIRA
ipen.date.recebimento20-09
ipen.identifier.fi4.411pt_BR
ipen.identifier.fiCiteScore4.7
ipen.identifier.ipendoc27181pt_BR
ipen.identifier.iwosWoSpt_BR
ipen.identifier.ods3
ipen.range.fi3.000 - 4.499
ipen.range.percentilfi50.00 - 74.99
ipen.type.genreArtigo
relation.isAuthorOfPublicationab78881a-78eb-42be-a463-aaf80e70de3d
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relation.isAuthorOfPublication.latestForDiscoveryf34ac8ed-8b5e-4916-9492-d6ee6c363ca0
sigepi.autor.atividadeBERNARDES, EMERSON S.:12099:110:Npt_BR
sigepi.autor.atividadePERINI, EFRAIN A.:9691:110:Npt_BR
sigepi.autor.atividadeNARIO, ARIAN P.:14076:110:Npt_BR
sigepi.autor.atividadeSANTOS, SOFIA N. dos:14464:110:Npt_BR
sigepi.autor.atividadePIJEIRA, MARTHA S.O.:14075:110:Spt_BR
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