Cargando…

Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes

Pathological blood clotting, or thrombosis, limits vital blood flow to organs; such deprivation can lead to catastrophic events including myocardial infarction, pulmonary embolism, and ischemic stroke. Prompt restoration of blood flow greatly improves outcomes. We explored whether aptamers could ser...

Descripción completa

Detalles Bibliográficos
Autores principales: Gray, Bethany Powell, Kelly, Linsley, Steen-Burrell, Kady-Ann, Layzer, Juliana M., Rempel, Rachel E., Nimjee, Shahid M., Cooley, Brian C., Tarantal, Alice F., Sullenger, Bruce A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930157/
https://www.ncbi.nlm.nih.gov/pubmed/36817726
http://dx.doi.org/10.1016/j.omtn.2023.01.009
_version_ 1784888998280298496
author Gray, Bethany Powell
Kelly, Linsley
Steen-Burrell, Kady-Ann
Layzer, Juliana M.
Rempel, Rachel E.
Nimjee, Shahid M.
Cooley, Brian C.
Tarantal, Alice F.
Sullenger, Bruce A.
author_facet Gray, Bethany Powell
Kelly, Linsley
Steen-Burrell, Kady-Ann
Layzer, Juliana M.
Rempel, Rachel E.
Nimjee, Shahid M.
Cooley, Brian C.
Tarantal, Alice F.
Sullenger, Bruce A.
author_sort Gray, Bethany Powell
collection PubMed
description Pathological blood clotting, or thrombosis, limits vital blood flow to organs; such deprivation can lead to catastrophic events including myocardial infarction, pulmonary embolism, and ischemic stroke. Prompt restoration of blood flow greatly improves outcomes. We explored whether aptamers could serve as molecular imaging probes to rapidly detect thrombi. An aptamer targeting thrombin, Tog25t, was found to rapidly localize to and visualize pre-existing clots in the femoral and jugular veins of mice using fluorescence imaging and, when circulating, was able to image clots as they form. Since free aptamer is quickly cleared from circulation, contrast is rapidly developed, allowing clot visualization within minutes. Moreover, administration of an antidote oligonucleotide further enhanced contrast development, causing the unbound aptamer to clear within 5min while impacting the clot-bound aptamer more slowly. These findings suggest that aptamers can serve as imaging agents for rapid detection of thrombi in acute care and perioperative settings.
format Online
Article
Text
id pubmed-9930157
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Society of Gene & Cell Therapy
record_format MEDLINE/PubMed
spelling pubmed-99301572023-02-16 Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes Gray, Bethany Powell Kelly, Linsley Steen-Burrell, Kady-Ann Layzer, Juliana M. Rempel, Rachel E. Nimjee, Shahid M. Cooley, Brian C. Tarantal, Alice F. Sullenger, Bruce A. Mol Ther Nucleic Acids Original Article Pathological blood clotting, or thrombosis, limits vital blood flow to organs; such deprivation can lead to catastrophic events including myocardial infarction, pulmonary embolism, and ischemic stroke. Prompt restoration of blood flow greatly improves outcomes. We explored whether aptamers could serve as molecular imaging probes to rapidly detect thrombi. An aptamer targeting thrombin, Tog25t, was found to rapidly localize to and visualize pre-existing clots in the femoral and jugular veins of mice using fluorescence imaging and, when circulating, was able to image clots as they form. Since free aptamer is quickly cleared from circulation, contrast is rapidly developed, allowing clot visualization within minutes. Moreover, administration of an antidote oligonucleotide further enhanced contrast development, causing the unbound aptamer to clear within 5min while impacting the clot-bound aptamer more slowly. These findings suggest that aptamers can serve as imaging agents for rapid detection of thrombi in acute care and perioperative settings. American Society of Gene & Cell Therapy 2023-01-21 /pmc/articles/PMC9930157/ /pubmed/36817726 http://dx.doi.org/10.1016/j.omtn.2023.01.009 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Gray, Bethany Powell
Kelly, Linsley
Steen-Burrell, Kady-Ann
Layzer, Juliana M.
Rempel, Rachel E.
Nimjee, Shahid M.
Cooley, Brian C.
Tarantal, Alice F.
Sullenger, Bruce A.
Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes
title Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes
title_full Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes
title_fullStr Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes
title_full_unstemmed Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes
title_short Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes
title_sort rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930157/
https://www.ncbi.nlm.nih.gov/pubmed/36817726
http://dx.doi.org/10.1016/j.omtn.2023.01.009
work_keys_str_mv AT graybethanypowell rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes
AT kellylinsley rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes
AT steenburrellkadyann rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes
AT layzerjulianam rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes
AT rempelrachele rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes
AT nimjeeshahidm rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes
AT cooleybrianc rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes
AT tarantalalicef rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes
AT sullengerbrucea rapidmolecularimagingofactivethrombiinvivousingaptamerantidoteprobes