# Direct Detection and Characterization of Thrombosis In Vivo

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $734,488

## Abstract

PROJECT SUMMARY / ABSTRACT
Vascular thrombosis is a major underlying factor in many cardiovascular, neurovascular, and related disorders,
and is a significant post-surgical complication. Current imaging modalities used to assess thrombotic events
present challenges because they primarily visualize the lack of blood flow rather than detailed information
about a thrombus directly, and they cannot distinguish between newly formed and aged blood clots. Our team
has previously demonstrated that high affinity and high specificity RNA aptamers can be generated against a
number of coagulation proteins including thrombin and factor IXa. In addition, our team has demonstrated that
aptamer-antidote pairs can be used as rapid binding-rapid reversal probes for real time detection of thrombi.
The studies proposed in this application integrate aptamer-antidote pairs with sensitive total-body positron
emission tomography (PET) imaging to develop a new approach in the way patients with thrombotic events
can be stratified and subsequently treated. This proposal represents the convergence of multidisciplinary
domains of expertise to explore a new team direction that will have a major impact on the field through the
following Specific Aims: (1) Develop and evaluate aptamer-antidote pairs to perform rapid imaging of thrombi in
mouse models for molecular thrombus profiling in vivo, and (2) Assess efficiency of radiolabeled aptamers for
total-body PET in nonhuman primates. Preliminary results have demonstrated that aptamers can rapidly bind
thrombin on active thrombi in vivo and that the antidotes can reverse such binding in under 5 minutes. In
Specific Aim 1, we will further develop this technology by conducting studies in mice with aptamer-antidote
pairs generated to thrombin, von Willebrand Factor, and platelet protein GPIIb/IIIa individually and combined.
Findings will be adapted in Specific Aim 2 to the translational rhesus monkey model system using total-body
PET that has demonstrated outstanding sensitivity. These investigations propose a new strategy to address
characterization of thrombi in vivo and include a multidisciplinary translational team with expertise in nucleic
acid biochemistry, combinatorial chemistry, antithrombotic agents, novel diagnostic imaging tools and
methods, and a nonhuman primate model system of profound translational importance.

## Key facts

- **NIH application ID:** 10438599
- **Project number:** 5R01HL147147-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** BRUCE ALAN SULLENGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $734,488
- **Award type:** 5
- **Project period:** 2019-07-22 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438599

## Citation

> US National Institutes of Health, RePORTER application 10438599, Direct Detection and Characterization of Thrombosis In Vivo (5R01HL147147-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10438599. Licensed CC0.

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