Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent

González, Joel - García, María Fernanda - Cabral González, Pablo - Calzada, Victoria - Cerecetto, Hugo

Resumen:

The goal of this work is to identify new fatty acid-mimetic 99mTc-complexes to be used as myocardial imaging agents that allow studying heart abnormalities in high-risk patients. In this sense, we designed a fatty acid-mimetic substructure including an amide moiety that, among other properties, could improve myocardial residence time. A diamide with a chain length of 15 atoms and porting a 6-hydrazinonicotinyl (HYNIC) chelator, and an analog with a short carbon-chain, were prepared with convergent organic synthetic procedures and radiolabeled with 99mTc using tricine as the sole coligand. The in vivo proofs of concept were performed using healthy mice. The new 99mTc-complexes were obtained with adequate radiochemical purity. The lipophilicities were in agreement with the length of the chains. While both 99mTccomplexes showed uptake in the myocardial muscle, the designed radiopharmaceutical with the longest chain length had preferential target-uptake and target-retention compared to other complexes described in the bibliography. Further studies, involving imaging assays, synthetic modifications, and assay of new coligands for 99mTc-HYNIC complexes, are currently ongoing.

Detalles Bibliográficos
2024
Technetium
Radiopharmaceutical
Myocardial metabolism
Long chain amide
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/50287
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)
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author González, Joel
author2 García, María Fernanda
Cabral González, Pablo
Calzada, Victoria
Cerecetto, Hugo
author2_role author
author
author
author
author_facet González, Joel
García, María Fernanda
Cabral González, Pablo
Calzada, Victoria
Cerecetto, Hugo
author_role author
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collection COLIBRI
dc.contributor.filiacion.none.fl_str_mv González Joel, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
García María Fernanda, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Cabral González Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.
Calzada Victoria, 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 González, Joel
García, María Fernanda
Cabral González, Pablo
Calzada, Victoria
Cerecetto, Hugo
dc.date.accessioned.none.fl_str_mv 2025-06-11T18:00:57Z
dc.date.available.none.fl_str_mv 2025-06-11T18:00:57Z
dc.date.issued.none.fl_str_mv 2024
dc.description.abstract.none.fl_txt_mv The goal of this work is to identify new fatty acid-mimetic 99mTc-complexes to be used as myocardial imaging agents that allow studying heart abnormalities in high-risk patients. In this sense, we designed a fatty acid-mimetic substructure including an amide moiety that, among other properties, could improve myocardial residence time. A diamide with a chain length of 15 atoms and porting a 6-hydrazinonicotinyl (HYNIC) chelator, and an analog with a short carbon-chain, were prepared with convergent organic synthetic procedures and radiolabeled with 99mTc using tricine as the sole coligand. The in vivo proofs of concept were performed using healthy mice. The new 99mTc-complexes were obtained with adequate radiochemical purity. The lipophilicities were in agreement with the length of the chains. While both 99mTccomplexes showed uptake in the myocardial muscle, the designed radiopharmaceutical with the longest chain length had preferential target-uptake and target-retention compared to other complexes described in the bibliography. Further studies, involving imaging assays, synthetic modifications, and assay of new coligands for 99mTc-HYNIC complexes, are currently ongoing.
dc.format.extent.es.fl_str_mv 13 h
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dc.identifier.citation.es.fl_str_mv González, J, García, M, Cabral González, P [y otros autores]. "Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent". Brazilian Journal of Pharmaceutical Sciences. [en línea] 2024, 60: e23542. 13 h. DOI: 10.1590/s2175-97902024e23542
dc.identifier.doi.none.fl_str_mv 10.1590/s2175-97902024e23542
dc.identifier.issn.none.fl_str_mv 2175-9790
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/50287
dc.language.iso.none.fl_str_mv en
eng
dc.publisher.es.fl_str_mv Universidade de São Paulo
dc.relation.none.fl_str_mv Brazilian Journal of Pharmaceutical Sciences, 2024, 60: e23542.
dc.rights.license.none.fl_str_mv Licencia Creative Commons Atribución (CC - By 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 Technetium
Radiopharmaceutical
Myocardial metabolism
Long chain amide
dc.title.none.fl_str_mv Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent
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 The goal of this work is to identify new fatty acid-mimetic 99mTc-complexes to be used as myocardial imaging agents that allow studying heart abnormalities in high-risk patients. In this sense, we designed a fatty acid-mimetic substructure including an amide moiety that, among other properties, could improve myocardial residence time. A diamide with a chain length of 15 atoms and porting a 6-hydrazinonicotinyl (HYNIC) chelator, and an analog with a short carbon-chain, were prepared with convergent organic synthetic procedures and radiolabeled with 99mTc using tricine as the sole coligand. The in vivo proofs of concept were performed using healthy mice. The new 99mTc-complexes were obtained with adequate radiochemical purity. The lipophilicities were in agreement with the length of the chains. While both 99mTccomplexes showed uptake in the myocardial muscle, the designed radiopharmaceutical with the longest chain length had preferential target-uptake and target-retention compared to other complexes described in the bibliography. Further studies, involving imaging assays, synthetic modifications, and assay of new coligands for 99mTc-HYNIC complexes, are currently ongoing.
eu_rights_str_mv openAccess
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id COLIBRI_877a90395a06f83435128e8a092e8d13
identifier_str_mv González, J, García, M, Cabral González, P [y otros autores]. "Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent". Brazilian Journal of Pharmaceutical Sciences. [en línea] 2024, 60: e23542. 13 h. DOI: 10.1590/s2175-97902024e23542
2175-9790
10.1590/s2175-97902024e23542
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:20.500.12008/50287
publishDate 2024
reponame_str COLIBRI
repository.mail.fl_str_mv karina.camps@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 (CC - By 4.0)
spelling González Joel, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.García María Fernanda, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Cabral González Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares.Calzada Victoria, 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.2025-06-11T18:00:57Z2025-06-11T18:00:57Z2024González, J, García, M, Cabral González, P [y otros autores]. "Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent". Brazilian Journal of Pharmaceutical Sciences. [en línea] 2024, 60: e23542. 13 h. DOI: 10.1590/s2175-97902024e235422175-9790https://hdl.handle.net/20.500.12008/5028710.1590/s2175-97902024e23542The goal of this work is to identify new fatty acid-mimetic 99mTc-complexes to be used as myocardial imaging agents that allow studying heart abnormalities in high-risk patients. In this sense, we designed a fatty acid-mimetic substructure including an amide moiety that, among other properties, could improve myocardial residence time. A diamide with a chain length of 15 atoms and porting a 6-hydrazinonicotinyl (HYNIC) chelator, and an analog with a short carbon-chain, were prepared with convergent organic synthetic procedures and radiolabeled with 99mTc using tricine as the sole coligand. The in vivo proofs of concept were performed using healthy mice. The new 99mTc-complexes were obtained with adequate radiochemical purity. The lipophilicities were in agreement with the length of the chains. While both 99mTccomplexes showed uptake in the myocardial muscle, the designed radiopharmaceutical with the longest chain length had preferential target-uptake and target-retention compared to other complexes described in the bibliography. Further studies, involving imaging assays, synthetic modifications, and assay of new coligands for 99mTc-HYNIC complexes, are currently ongoing.Submitted by Pintos Natalia (nataliapintosmvd@gmail.com) on 2025-06-10T18:04:34Z No. of bitstreams: 2 license_rdf: 24942 bytes, checksum: 58cb336ce230a47d2f88ad02838a665f (MD5) 10.1590-s2175-97902024e23542.pdf: 1061215 bytes, checksum: 258809abba2b4a0c182c94e5a634e052 (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2025-06-11T14:31:07Z (GMT) No. of bitstreams: 2 license_rdf: 24942 bytes, checksum: 58cb336ce230a47d2f88ad02838a665f (MD5) 10.1590-s2175-97902024e23542.pdf: 1061215 bytes, checksum: 258809abba2b4a0c182c94e5a634e052 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2025-06-11T18:00:57Z (GMT). No. of bitstreams: 2 license_rdf: 24942 bytes, checksum: 58cb336ce230a47d2f88ad02838a665f (MD5) 10.1590-s2175-97902024e23542.pdf: 1061215 bytes, checksum: 258809abba2b4a0c182c94e5a634e052 (MD5) Previous issue date: 202413 happlication/pdfenengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences, 2024, 60: e23542.Las 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 (CC - By 4.0)TechnetiumRadiopharmaceuticalMyocardial metabolismLong chain amideDesign and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agentArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaGonzález, JoelGarcía, María FernandaCabral González, PabloCalzada, VictoriaCerecetto, HugoLICENSElicense.txtlicense.txttext/plain; charset=utf-84267http://localhost:8080/xmlui/bitstream/20.500.12008/50287/5/license.txt6429389a7df7277b72b7924fdc7d47a9MD55CC-LICENSElicense_urllicense_urltext/plain; charset=utf-844http://localhost:8080/xmlui/bitstream/20.500.12008/50287/2/license_urla0ebbeafb9d2ec7cbb19d7137ebc392cMD52license_textlicense_texttext/html; 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- Universidad de la Repúblicafalse
spellingShingle Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent
González, Joel
Technetium
Radiopharmaceutical
Myocardial metabolism
Long chain amide
status_str publishedVersion
title Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent
title_full Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent
title_fullStr Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent
title_full_unstemmed Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent
title_short Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent
title_sort Design and development of 6-hydrazinonicotinylfatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent
topic Technetium
Radiopharmaceutical
Myocardial metabolism
Long chain amide
url https://hdl.handle.net/20.500.12008/50287