title: Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of Thrombosis.
abstract: BACKGROUND
  Myocardial infarction and stroke are leading causes of morbidity/mortality. The typical underlying pathology is the formation of thrombi/emboli and subsequent vessel occlusion. Systemically administered fibrinolytic drugs are the most effective pharmacological therapy. However, bleeding complications are relatively common and this risk as such limits their broader use. Furthermore, a rapid non-invasive imaging technology is not available. Thereby, many thrombotic events are missed or only diagnosed when ischemic damage has already occurred.
  
  
  OBJECTIVE
  Design and preclinical testing of a novel 'theranostic' technology for the rapid non-invasive diagnosis and effective, bleeding-free treatment of thrombosis.
  
  
  RESULTS
  A newly created, innovative theranostic microbubble combines a recombinant fibrinolytic drug, an echo-enhancing microbubble and a recombinant thrombus-targeting device in form of an activated-platelet-specific single-chain antibody. After initial in vitro proof of functionality, we tested this theranostic microbubble both in ultrasound imaging and thrombolytic therapy using a mouse model of ferric-chloride-induced thrombosis in the carotid artery. We demonstrate the reliable highly sensitive detection of in vivo thrombi and the ability to monitor their size changes in real time. Furthermore, these theranostic microbubbles proofed to be as effective in thrombolysis as commercial urokinase but without the prolongation of bleeding time as seen with urokinase.
  
  
  CONCLUSIONS
  We describe a novel theranostic technology enabling simultaneous diagnosis and treatment of thrombosis, as well as monitoring of success or failure of thrombolysis. This technology holds promise for major progress in rapid diagnosis and bleeding-free thrombolysis thereby potentially preventing the often devastating consequences of thrombotic disease in many patients.
authors.affiliation: 1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.; 2. Department of Medicine, Monash University, Melbourne, Australia.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.; 3. Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Yannik
authors.initials: Y
authors.lastname: Gkanatsas
authors.affiliation: 1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Jathushan
authors.initials: J
authors.lastname: Palasubramaniam
authors.affiliation: 1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Jan David
authors.initials: JD
authors.lastname: Hohmann
authors.affiliation: 1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Yung Chih
authors.initials: YC
authors.lastname: Chen
authors.affiliation: 1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Bock
authors.initials: B
authors.lastname: Lim
authors.affiliation: 1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.; 4. Department of Immunology, Monash University, Melbourne, Australia.
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Hagemeyer
authors.affiliation: 1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.; 2. Department of Medicine, Monash University, Melbourne, Australia.; 4. Department of Immunology, Monash University, Melbourne, Australia.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000276:immunology; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D045423:Microbubbles; D057127:Single-Chain Antibodies / Q000276:immunology / Q000493:pharmacokinetics; D000068936:Theranostic Nanomedicine / Q000379:methods*; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000000981:diagnostic imaging* / Q000628:therapy*; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods*
chemical_list: D005343:Fibrinolytic Agents; D057127:Single-Chain Antibodies
keywords: glycoprotein IIb/IIIa; microbubbles.; platelets; theranostics; thrombolysis