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

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

doi:10.1016/j.omtn.2023.01.009

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

Mol Ther Nucleic Acids. 2023 Jan 21:31:440-451. doi: 10.1016/j.omtn.2023.01.009. eCollection 2023 Mar 14.

Authors

Bethany Powell Gray¹, Linsley Kelly¹, Kady-Ann Steen-Burrell¹, Juliana M Layzer¹, Rachel E Rempel¹, Shahid M Nimjee², Brian C Cooley³, Alice F Tarantal⁴, Bruce A Sullenger^{1

5}

Affiliations

¹ Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
² Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
³ Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7525, USA.
⁴ Departments 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, USA.
⁵ Departments of Pharmacology & Cancer Biology and Biomedical Engineering, Duke University, Durham, NC 27710, USA.

Abstract

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.

Keywords: MT: Oligonucleotides: Diagnostics and Biosensors; RNA; aptamers; clot imaging; imaging; thrombosis.

Abstract

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