BINDING AND LYSING OF BLOOD-CLOTS USING MRX-408

RATIONALE AND OBJECTIVES. A thrombus-specific ultrasound contrast agen t, MRX-408, has been developed recently. This agent consists of phosph olipid-coated microbubbles with a ligand capable of targeting the GPll b/IIIa receptor, thereby allowing the microbubbles to bind with thromb i rich in activated platelets, In vitro and in vivo animal experiments have been conducted to examine imaging enhancement and sonothrombulys is using this agent compared with a nontargeted agent, METHODS. For cl ot binding, blood-smeared slides were incubated with microbubbles and examined under a light microscope, Change in backscatter signals from the:blood clots after binding was examined by both an ultrasound scann er and two single-element transducers arranged in a transmitter-receiv er pair. For clot lysis, either 1-MHz or 20-KHz ultrasound was used to enhance the lysing effects of MRX-408 with or without urokinase, RESU LTS. Evidence of binding was demonstrated under a microscope. In vitro experiments showed that the ''acoustic signature,'' or properties, of blood clots changed after binding. Clots became more echogenic and no nlinear. In vivo fundamental ultrasound imaging confirmed that as a re sult of binding, blood clots were more visible, the area of detection was improved, and shadowing behind clots was more noticeable, Under 1- MHz ultrasound and 30 minutes of treatment, lysis efficiency reached 3 4% with MRX-408, whereas there was no visible clot lysis with saline. CONCLUSION. The results of these preliminary studies show that as a co ntrast agent, MRX-408 enhanced clots under ultrasound imaging and faci litated sonothrombolysis with or without thrombolytic drugs.