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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253123000124 |
| _version_ | 1797924693635760128 |
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| author | Bethany Powell Gray Linsley Kelly Kady-Ann Steen-Burrell Juliana M. Layzer Rachel E. Rempel Shahid M. Nimjee Brian C. Cooley Alice F. Tarantal Bruce A. Sullenger |
| author_facet | Bethany Powell Gray Linsley Kelly Kady-Ann Steen-Burrell Juliana M. Layzer Rachel E. Rempel Shahid M. Nimjee Brian C. Cooley Alice F. Tarantal Bruce A. Sullenger |
| author_sort | Bethany Powell Gray |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-10T15:06:07Z |
| format | Article |
| id | doaj.art-1ee17a94201144fc8700f739b611a006 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-10T15:06:07Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-1ee17a94201144fc8700f739b611a0062023-02-15T04:27:49ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-03-0131440451Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probesBethany Powell Gray0Linsley Kelly1Kady-Ann Steen-Burrell2Juliana M. Layzer3Rachel E. Rempel4Shahid M. Nimjee5Brian C. Cooley6Alice F. Tarantal7Bruce A. Sullenger8Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USADepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USADepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USADepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USADepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USADepartment of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USADepartment of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7525, USADepartments of Pediatrics and Cell Biology and Human Anatomy, School of Medicine, and California National Primate Research Center, University of California Davis, Davis, CA 95616-8542, USADepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Departments of Pharmacology & Cancer Biology and Biomedical Engineering, Duke University, Durham, NC 27710, USA; Corresponding author: Bruce A. Sullenger, Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.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.http://www.sciencedirect.com/science/article/pii/S2162253123000124MT: Oligonucleotides: Diagnostics and BiosensorsaptamersRNAimagingthrombosisclot imaging |
| spellingShingle | Bethany Powell Gray Linsley Kelly Kady-Ann Steen-Burrell Juliana M. Layzer Rachel E. Rempel Shahid M. Nimjee Brian C. Cooley Alice F. Tarantal Bruce A. Sullenger Rapid molecular imaging of active thrombi in vivo using aptamer-antidote probes Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Diagnostics and Biosensors aptamers RNA imaging thrombosis clot imaging |
| 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 | MT: Oligonucleotides: Diagnostics and Biosensors aptamers RNA imaging thrombosis clot imaging |
| url | http://www.sciencedirect.com/science/article/pii/S2162253123000124 |
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