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    Highly Sensitive Detection of Minimal Cardiac Ischemia using Positron Emission Tomography Imaging of Activated Platelets

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    Author
    Ziegler, M; Alt, K; Paterson, BM; Kanellakis, P; Bobik, A; Donnelly, PS; Hagemeyer, CE; Peter, K
    Date
    2016-12-02
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Paterson, Brett; Donnelly, Paul; Peter, Karlheinz
    Affiliation
    School of Chemistry
    Melbourne Medical School
    Metadata
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    Document Type
    Journal Article
    Citations
    Ziegler, M., Alt, K., Paterson, B. M., Kanellakis, P., Bobik, A., Donnelly, P. S., Hagemeyer, C. E. & Peter, K. (2016). Highly Sensitive Detection of Minimal Cardiac Ischemia using Positron Emission Tomography Imaging of Activated Platelets. SCIENTIFIC REPORTS, 6 (1), https://doi.org/10.1038/srep38161.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257354
    DOI
    10.1038/srep38161
    Abstract
    A reliable method for the diagnosis of minimal cardiac ischemia would meet a strong demand for the sensitive diagnosis of coronary artery disease in cardiac stress testing and risk stratification in patients with chest pain but unremarkable ECGs and biomarkers. We hypothesized that platelets accumulate early on in ischemic myocardium and a newly developed technology of non-invasive molecular PET imaging of activated platelets can thus detect minimal degrees of myocardial ischemia. To induce different degrees of minimal cardiac ischemia, the left anterior descending artery (LAD) was ligated for 10, 20 or 60 min. Mice were injected with a newly generated scFvanti-GPIIb/IIIa-64CuMeCOSar radiotracer, composed of a single-chain antibody that only binds to activated integrin GPIIb/IIIa (αIIbβIII) and thus to activated platelets, and a sarcophagine cage MeCOSar complexing the long half-life PET tracer copper-64. A single PET/CT scan was performed. Evans Blue/TTC staining to detect necrosis as well as classical serological biomarkers like Troponin I and heart-type fatty acid-binding protein (H-FABP) were negative, whereas PET imaging of activated platelets was able to detect small degrees of ischemia. Taken together, molecular PET imaging of activated platelets represents a unique and highly sensitive method to detect minimal cardiac ischemia.

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