Theranostics 2016; 6(5):726-738. doi:10.7150/thno.14514

Research Paper

Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of Thrombosis

Xiaowei Wang1,2✉*, Yannik Gkanatsas1,3✉*, Jathushan Palasubramaniam1, Jan David Hohmann1, Yung Chih Chen1, Bock Lim1, Christoph E Hagemeyer1,4, Karlheinz Peter1,2,4

1. Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
2. Department of Medicine, Monash University, Melbourne, Australia.
3. Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
4. Department of Immunology, Monash University, Melbourne, Australia.
*Equally contributing first authors.

Abstract

Rationale: 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.

Methods and 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.

Keywords: platelets, theranostics, thrombolysis, glycoprotein IIb/IIIa, microbubbles.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Wang X, Gkanatsas Y, Palasubramaniam J, Hohmann JD, Chen YC, Lim B, Hagemeyer CE, Peter K. Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of Thrombosis. Theranostics 2016; 6(5):726-738. doi:10.7150/thno.14514. Available from http://www.thno.org/v06p0726.htm