Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga

Calzada, Victoria - Báez, Jessica - Sicco, Estefanía - Margenat, Jimena - Fernández, Marcelo - Moreno, María - Ibarra, Manuel - Gambini, Juan Pablo - Cabral González, Pablo - Cerecetto, Hugo

Resumen:

Nucleic acid aptamers can recognise their target with high affinity and specificity, and their potential as molecular imaging agents and use in theranostics are being explored. Compared with antibodies, aptamers can be easily synthesized and chemically modified, rendering them a valuable tool for in vivo approaches. Herein, we investigated a 41nt DNA aptamer as a theranostic agent for lymphoma and melanoma. This aptamer exhibits specific binding and high affinity for the PTK7 receptor that is overexpressed in many cancer cells. A 5’-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator DOTA (1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) and labelled with the radionuclide 67Ga, forming the aptamer probe Sgc8- c-DOTA-67Ga. Different conditions during synthesis, purification and identification of the intermediate and final radiolabelled probe, were examined. Aptamer modification and radiolabelling were performed with high yields, resulting in a probe that was stable in neutral buffered solution. Binding to PTK7 was studied in CCRFCEM, A20 and B16F1 cell lines, and in purified PTK7-1 receptor, to confirm specificity. The in vitro cell lines showed different levels of uptake, and the signal increased over time. In vivo binding properties were studied in A20 and B16F10 tumour-bearing mice and images were acquired using X-rays and gamma imaging modalities for both models. Preliminary results in both tumour models showed good aptamer uptake by tumour. Hepatobiliar metabolism was observed with Sgc8-c-DOTA-67Ga and no signal was detected in normal tissue. In summary, these results support the utility of labelled aptamers as theranostic agents in different imaging modalities and theranostic.


Detalles Bibliográficos
2017
Aptamer
Sgc8-c
PTK7
Molecular imaging
Theranostic
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/24810
Acceso abierto
Licencia Creative Commons Atribución - No Comercial (CC - By-NC 4.0)
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author Calzada, Victoria
author2 Báez, Jessica
Sicco, Estefanía
Margenat, Jimena
Fernández, Marcelo
Moreno, María
Ibarra, Manuel
Gambini, Juan Pablo
Cabral González, Pablo
Cerecetto, Hugo
author2_role author
author
author
author
author
author
author
author
author
author_facet Calzada, Victoria
Báez, Jessica
Sicco, Estefanía
Margenat, Jimena
Fernández, Marcelo
Moreno, María
Ibarra, Manuel
Gambini, Juan Pablo
Cabral González, Pablo
Cerecetto, Hugo
author_role author
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collection COLIBRI
dc.contributor.filiacion.none.fl_str_mv Calzada Victoria, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Báez Jessica, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Sicco Estefanía, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Margenat Jimena, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Fernández Marcelo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Moreno María, Universidad de la República (Uruguay). Facultad de Medicina
Ibarra Manuel, Universidad de la República (Uruguay). Facultad de Química
Gambini Juan Pablo, Universidad de la República (Uruguay). Hospital de Clínicas
Cabral González, Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Cerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
dc.creator.none.fl_str_mv Calzada, Victoria
Báez, Jessica
Sicco, Estefanía
Margenat, Jimena
Fernández, Marcelo
Moreno, María
Ibarra, Manuel
Gambini, Juan Pablo
Cabral González, Pablo
Cerecetto, Hugo
dc.date.accessioned.none.fl_str_mv 2020-07-28T18:40:16Z
dc.date.available.none.fl_str_mv 2020-07-28T18:40:16Z
dc.date.issued.none.fl_str_mv 2017
dc.description.abstract.none.fl_txt_mv Nucleic acid aptamers can recognise their target with high affinity and specificity, and their potential as molecular imaging agents and use in theranostics are being explored. Compared with antibodies, aptamers can be easily synthesized and chemically modified, rendering them a valuable tool for in vivo approaches. Herein, we investigated a 41nt DNA aptamer as a theranostic agent for lymphoma and melanoma. This aptamer exhibits specific binding and high affinity for the PTK7 receptor that is overexpressed in many cancer cells. A 5’-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator DOTA (1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) and labelled with the radionuclide 67Ga, forming the aptamer probe Sgc8- c-DOTA-67Ga. Different conditions during synthesis, purification and identification of the intermediate and final radiolabelled probe, were examined. Aptamer modification and radiolabelling were performed with high yields, resulting in a probe that was stable in neutral buffered solution. Binding to PTK7 was studied in CCRFCEM, A20 and B16F1 cell lines, and in purified PTK7-1 receptor, to confirm specificity. The in vitro cell lines showed different levels of uptake, and the signal increased over time. In vivo binding properties were studied in A20 and B16F10 tumour-bearing mice and images were acquired using X-rays and gamma imaging modalities for both models. Preliminary results in both tumour models showed good aptamer uptake by tumour. Hepatobiliar metabolism was observed with Sgc8-c-DOTA-67Ga and no signal was detected in normal tissue. In summary, these results support the utility of labelled aptamers as theranostic agents in different imaging modalities and theranostic.
dc.format.extent.es.fl_str_mv 9 h
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dc.identifier.citation.es.fl_str_mv Calzada, V, Báez, J, Sicco, E, y otros. "Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga". Aptamers. [en línea] 2017, 1: 19–27. 9 h.
dc.identifier.issn.none.fl_str_mv 2514-3247
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/24810
dc.language.iso.none.fl_str_mv en
eng
dc.publisher.es.fl_str_mv International Society on Aptamers
dc.relation.ispartof.es.fl_str_mv Aptamers, 2017, 1: 19–27
dc.rights.license.none.fl_str_mv Licencia Creative Commons Atribución - No Comercial (CC - By-NC 4.0)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.es.fl_str_mv Aptamer
Sgc8-c
PTK7
Molecular imaging
Theranostic
dc.title.none.fl_str_mv Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
dc.type.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
description Nucleic acid aptamers can recognise their target with high affinity and specificity, and their potential as molecular imaging agents and use in theranostics are being explored. Compared with antibodies, aptamers can be easily synthesized and chemically modified, rendering them a valuable tool for in vivo approaches. Herein, we investigated a 41nt DNA aptamer as a theranostic agent for lymphoma and melanoma. This aptamer exhibits specific binding and high affinity for the PTK7 receptor that is overexpressed in many cancer cells. A 5’-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator DOTA (1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) and labelled with the radionuclide 67Ga, forming the aptamer probe Sgc8- c-DOTA-67Ga. Different conditions during synthesis, purification and identification of the intermediate and final radiolabelled probe, were examined. Aptamer modification and radiolabelling were performed with high yields, resulting in a probe that was stable in neutral buffered solution. Binding to PTK7 was studied in CCRFCEM, A20 and B16F1 cell lines, and in purified PTK7-1 receptor, to confirm specificity. The in vitro cell lines showed different levels of uptake, and the signal increased over time. In vivo binding properties were studied in A20 and B16F10 tumour-bearing mice and images were acquired using X-rays and gamma imaging modalities for both models. Preliminary results in both tumour models showed good aptamer uptake by tumour. Hepatobiliar metabolism was observed with Sgc8-c-DOTA-67Ga and no signal was detected in normal tissue. In summary, these results support the utility of labelled aptamers as theranostic agents in different imaging modalities and theranostic.
eu_rights_str_mv openAccess
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identifier_str_mv Calzada, V, Báez, J, Sicco, E, y otros. "Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga". Aptamers. [en línea] 2017, 1: 19–27. 9 h.
2514-3247
instacron_str Universidad de la República
institution Universidad de la República
instname_str Universidad de la República
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network_acronym_str COLIBRI
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publishDate 2017
reponame_str COLIBRI
repository.mail.fl_str_mv mabel.seroubian@seciu.edu.uy
repository.name.fl_str_mv COLIBRI - Universidad de la República
repository_id_str 4771
rights_invalid_str_mv Licencia Creative Commons Atribución - No Comercial (CC - By-NC 4.0)
spelling Calzada Victoria, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Báez Jessica, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Sicco Estefanía, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Margenat Jimena, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Fernández Marcelo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Moreno María, Universidad de la República (Uruguay). Facultad de MedicinaIbarra Manuel, Universidad de la República (Uruguay). Facultad de QuímicaGambini Juan Pablo, Universidad de la República (Uruguay). Hospital de ClínicasCabral González, Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Cerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.2020-07-28T18:40:16Z2020-07-28T18:40:16Z2017Calzada, V, Báez, J, Sicco, E, y otros. "Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga". Aptamers. [en línea] 2017, 1: 19–27. 9 h.2514-3247https://hdl.handle.net/20.500.12008/24810Nucleic acid aptamers can recognise their target with high affinity and specificity, and their potential as molecular imaging agents and use in theranostics are being explored. Compared with antibodies, aptamers can be easily synthesized and chemically modified, rendering them a valuable tool for in vivo approaches. Herein, we investigated a 41nt DNA aptamer as a theranostic agent for lymphoma and melanoma. This aptamer exhibits specific binding and high affinity for the PTK7 receptor that is overexpressed in many cancer cells. A 5’-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator DOTA (1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) and labelled with the radionuclide 67Ga, forming the aptamer probe Sgc8- c-DOTA-67Ga. Different conditions during synthesis, purification and identification of the intermediate and final radiolabelled probe, were examined. Aptamer modification and radiolabelling were performed with high yields, resulting in a probe that was stable in neutral buffered solution. Binding to PTK7 was studied in CCRFCEM, A20 and B16F1 cell lines, and in purified PTK7-1 receptor, to confirm specificity. The in vitro cell lines showed different levels of uptake, and the signal increased over time. In vivo binding properties were studied in A20 and B16F10 tumour-bearing mice and images were acquired using X-rays and gamma imaging modalities for both models. Preliminary results in both tumour models showed good aptamer uptake by tumour. Hepatobiliar metabolism was observed with Sgc8-c-DOTA-67Ga and no signal was detected in normal tissue. In summary, these results support the utility of labelled aptamers as theranostic agents in different imaging modalities and theranostic.Submitted by Faget Cecilia (lfaget@fcien.edu.uy) on 2020-07-28T14:25:16Z No. of bitstreams: 2 license_rdf: 21687 bytes, checksum: 749156fd3854beb422ddf543c77fb5b1 (MD5) Cab2017PRE.pdf: 983380 bytes, checksum: 44ed96943aa718101d92e1788d8fa334 (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2020-07-28T14:30:28Z (GMT) No. of bitstreams: 2 license_rdf: 21687 bytes, checksum: 749156fd3854beb422ddf543c77fb5b1 (MD5) Cab2017PRE.pdf: 983380 bytes, checksum: 44ed96943aa718101d92e1788d8fa334 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@fic.edu.uy) on 2020-07-28T18:40:16Z (GMT). No. of bitstreams: 2 license_rdf: 21687 bytes, checksum: 749156fd3854beb422ddf543c77fb5b1 (MD5) Cab2017PRE.pdf: 983380 bytes, checksum: 44ed96943aa718101d92e1788d8fa334 (MD5) Previous issue date: 20179 happlication/pdfenengInternational Society on AptamersAptamers, 2017, 1: 19–27Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución - No Comercial (CC - By-NC 4.0)AptamerSgc8-cPTK7Molecular imagingTheranosticPreliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67GaArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaCalzada, VictoriaBáez, JessicaSicco, EstefaníaMargenat, JimenaFernández, MarceloMoreno, MaríaIbarra, ManuelGambini, Juan PabloCabral González, PabloCerecetto, HugoLICENSElicense.txtlicense.txttext/plain; charset=utf-84267http://localhost:8080/xmlui/bitstream/20.500.12008/24810/5/license.txt6429389a7df7277b72b7924fdc7d47a9MD55CC-LICENSElicense_urllicense_urltext/plain; charset=utf-847http://localhost:8080/xmlui/bitstream/20.500.12008/24810/2/license_url966d4a1cc97b2c4389b5142dd97d3c7fMD52license_textlicense_texttext/html; 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- Universidad de la Repúblicafalse
spellingShingle Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
Calzada, Victoria
Aptamer
Sgc8-c
PTK7
Molecular imaging
Theranostic
status_str publishedVersion
title Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
title_full Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
title_fullStr Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
title_full_unstemmed Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
title_short Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
title_sort Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
topic Aptamer
Sgc8-c
PTK7
Molecular imaging
Theranostic
url https://hdl.handle.net/20.500.12008/24810