Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/5960 |
Resumo: | The characterization of a new class of hydrophilic liver-targeted agents for gamma-scintigraphy and MRI, consisting, respectively, of [153Sm]3+ or Gd3+ complexes of DOTA monoamide or bisamide linked glycoconjugates (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), is reported. In vitro studies show high uptake of radiolabeled 153SmDOTAGal2 by the human hepatocyte carcinoma cell line Hep G2 containing the asialoglycoprotein receptor (ASGP-R), which is decreased to less than 50 % by the presence of its high affinity ligand asialofetuin (ASF). In vivo biodistribution, gamma-imaging and pharmaco-kinetic studies on Wistar rats using the [153Sm]3+-radiolabeled conjugates show an high uptake in the receptor-rich organ liver of the compounds containing terminal galactosyl groups, but very little uptake for those with terminal glycosyl groups. Blocking the receptor in vivo reduced liver uptake by 90%, strongly suggesting that the liver uptake of these compounds is mediated by their binding to the asyaloglycoprotein receptor (ASGP-R). This study also demonstrated that the valency increase improves the targeting capability of the glycoconjugates, which is also affected by their topology. However despite the specific liver uptake of the radiolabeled galactose-bearing multivalent compounds, the animal MRI assessment of the corresponding Gd3+ chelates shows liver-to-kidney contrast effects which are not significantly better than those shown by GdDTPA. The maximum concentration/dose ratio attained in the kidneys by the Gd3+- based CAs is considerably lower than for GdDTPA, indicating that part of the injected CAs is T1 contrast-silent, presumably when taken up into the liver. The T1 shortening effect of the Gd3+-labeled Gal-containing compounds is probably strongly diminished upon hepatocyte internalization into an endossomic vesicle via receptor-mediated endocytosis of the ASGP-R. |
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Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studiesMagnetic resonance imagingContrast agentsGadoliniumGlycoconjugatesLiver targetingAsialoglycoprotein receptorGamma imaginggamma scintigraphyScience & TechnologyThe characterization of a new class of hydrophilic liver-targeted agents for gamma-scintigraphy and MRI, consisting, respectively, of [153Sm]3+ or Gd3+ complexes of DOTA monoamide or bisamide linked glycoconjugates (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), is reported. In vitro studies show high uptake of radiolabeled 153SmDOTAGal2 by the human hepatocyte carcinoma cell line Hep G2 containing the asialoglycoprotein receptor (ASGP-R), which is decreased to less than 50 % by the presence of its high affinity ligand asialofetuin (ASF). In vivo biodistribution, gamma-imaging and pharmaco-kinetic studies on Wistar rats using the [153Sm]3+-radiolabeled conjugates show an high uptake in the receptor-rich organ liver of the compounds containing terminal galactosyl groups, but very little uptake for those with terminal glycosyl groups. Blocking the receptor in vivo reduced liver uptake by 90%, strongly suggesting that the liver uptake of these compounds is mediated by their binding to the asyaloglycoprotein receptor (ASGP-R). This study also demonstrated that the valency increase improves the targeting capability of the glycoconjugates, which is also affected by their topology. However despite the specific liver uptake of the radiolabeled galactose-bearing multivalent compounds, the animal MRI assessment of the corresponding Gd3+ chelates shows liver-to-kidney contrast effects which are not significantly better than those shown by GdDTPA. The maximum concentration/dose ratio attained in the kidneys by the Gd3+- based CAs is considerably lower than for GdDTPA, indicating that part of the injected CAs is T1 contrast-silent, presumably when taken up into the liver. The T1 shortening effect of the Gd3+-labeled Gal-containing compounds is probably strongly diminished upon hepatocyte internalization into an endossomic vesicle via receptor-mediated endocytosis of the ASGP-R.Fundação para a Ciência e Tecnologia (FCT) -POCTI/QUI/47005/2002.III Instituto de Investigação Interdisciplinar University of Coimbra - III/BIO/45/2005.Institut of Health Carlos III (Spain) - PIO051845.FEDER.WileyUniversidade do MinhoPrata, M. I. M.Santos, A. C.Torres, SusanaAndré, João P.Martins, J. A. R.Neves, M.García Martín, M. L.Rodrigues, T. B.López Larrubia, P.Cerdán, S.Geraldes, Carlos F. G. C.2006-122006-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/1822/5960eng"Contrast Media & Molecular Imaging". ISSN 1555-4309.1 (2006) 246-258.1555-430910.1002/cmmi.111http://www3.interscience.wiley.com/cgi-bin/fulltext/113411803/PDFSTARTwww.interscience.wiley.cominfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T11:55:16Zoai:repositorium.sdum.uminho.pt:1822/5960Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:44:48.411258Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies |
title |
Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies |
spellingShingle |
Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies Prata, M. I. M. Magnetic resonance imaging Contrast agents Gadolinium Glycoconjugates Liver targeting Asialoglycoprotein receptor Gamma imaging gamma scintigraphy Science & Technology |
title_short |
Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies |
title_full |
Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies |
title_fullStr |
Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies |
title_full_unstemmed |
Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies |
title_sort |
Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies |
author |
Prata, M. I. M. |
author_facet |
Prata, M. I. M. Santos, A. C. Torres, Susana André, João P. Martins, J. A. R. Neves, M. García Martín, M. L. Rodrigues, T. B. López Larrubia, P. Cerdán, S. Geraldes, Carlos F. G. C. |
author_role |
author |
author2 |
Santos, A. C. Torres, Susana André, João P. Martins, J. A. R. Neves, M. García Martín, M. L. Rodrigues, T. B. López Larrubia, P. Cerdán, S. Geraldes, Carlos F. G. C. |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Prata, M. I. M. Santos, A. C. Torres, Susana André, João P. Martins, J. A. R. Neves, M. García Martín, M. L. Rodrigues, T. B. López Larrubia, P. Cerdán, S. Geraldes, Carlos F. G. C. |
dc.subject.por.fl_str_mv |
Magnetic resonance imaging Contrast agents Gadolinium Glycoconjugates Liver targeting Asialoglycoprotein receptor Gamma imaging gamma scintigraphy Science & Technology |
topic |
Magnetic resonance imaging Contrast agents Gadolinium Glycoconjugates Liver targeting Asialoglycoprotein receptor Gamma imaging gamma scintigraphy Science & Technology |
description |
The characterization of a new class of hydrophilic liver-targeted agents for gamma-scintigraphy and MRI, consisting, respectively, of [153Sm]3+ or Gd3+ complexes of DOTA monoamide or bisamide linked glycoconjugates (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), is reported. In vitro studies show high uptake of radiolabeled 153SmDOTAGal2 by the human hepatocyte carcinoma cell line Hep G2 containing the asialoglycoprotein receptor (ASGP-R), which is decreased to less than 50 % by the presence of its high affinity ligand asialofetuin (ASF). In vivo biodistribution, gamma-imaging and pharmaco-kinetic studies on Wistar rats using the [153Sm]3+-radiolabeled conjugates show an high uptake in the receptor-rich organ liver of the compounds containing terminal galactosyl groups, but very little uptake for those with terminal glycosyl groups. Blocking the receptor in vivo reduced liver uptake by 90%, strongly suggesting that the liver uptake of these compounds is mediated by their binding to the asyaloglycoprotein receptor (ASGP-R). This study also demonstrated that the valency increase improves the targeting capability of the glycoconjugates, which is also affected by their topology. However despite the specific liver uptake of the radiolabeled galactose-bearing multivalent compounds, the animal MRI assessment of the corresponding Gd3+ chelates shows liver-to-kidney contrast effects which are not significantly better than those shown by GdDTPA. The maximum concentration/dose ratio attained in the kidneys by the Gd3+- based CAs is considerably lower than for GdDTPA, indicating that part of the injected CAs is T1 contrast-silent, presumably when taken up into the liver. The T1 shortening effect of the Gd3+-labeled Gal-containing compounds is probably strongly diminished upon hepatocyte internalization into an endossomic vesicle via receptor-mediated endocytosis of the ASGP-R. |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006-12 2006-12-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/5960 |
url |
http://hdl.handle.net/1822/5960 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
"Contrast Media & Molecular Imaging". ISSN 1555-4309.1 (2006) 246-258. 1555-4309 10.1002/cmmi.111 http://www3.interscience.wiley.com/cgi-bin/fulltext/113411803/PDFSTART www.interscience.wiley.com |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132198637404160 |