Preliminary in vivo characterization of a theranostic aptamer: Sgc8-c- DOTA-67Ga
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.
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 |
dc.format.mimetype.es.fl_str_mv | application/pdf |
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 |
format | article |
id | COLIBRI_ab96dc63e67e426da26fce5b3a92142f |
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 |
language | eng |
language_invalid_str_mv | en |
network_acronym_str | COLIBRI |
network_name_str | COLIBRI |
oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/24810 |
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 |