title: Highly Sensitive Detection of Minimal Cardiac Ischemia using Positron Emission Tomography Imaging of Activated Platelets.
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.
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart &Diabetes Institute, Melbourne, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ziegler
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart &Diabetes Institute, Melbourne, Australia.|Vascular Biotechnology, Baker IDI Heart &Diabetes Institute, Melbourne, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Alt
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Australia.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Paterson
authors.affiliation: Vascular Biology &Atherosclerosis, Baker IDI Heart &Diabetes Institute, Melbourne, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Kanellakis
authors.affiliation: Vascular Biology &Atherosclerosis, Baker IDI Heart &Diabetes Institute, Melbourne, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Bobik
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Donnelly
authors.affiliation: Vascular Biotechnology, Baker IDI Heart &Diabetes Institute, Melbourne, Australia.|Central Clinical School, Monash University, Melbourne, Australia.|RMIT University, Melbourne, Australia.
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Hagemeyer
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart &Diabetes Institute, Melbourne, Australia.|Central Clinical School, Monash University, Melbourne, Australia.|RMIT University, Melbourne, Australia.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000818:Animals; D001792:Blood Platelets; D003287:Contrast Media / Q000494:pharmacology*; D017023:Coronary Angiography / Q000379:methods*; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging*; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D049268:Positron-Emission Tomography / Q000379:methods*; D057127:Single-Chain Antibodies / Q000494:pharmacology*
chemical_list: D003287:Contrast Media; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D057127:Single-Chain Antibodies