In vivo clot lysis of human thrombus with intravenous abciximab immunobubbles and ultrasound.
Abciximab immunobubbles have been introduced recently for ultrasonographic molecular imaging of human thrombus. This study investigates the potential of using these novel bubbles for enhancing sonothrombolysis. In particular, it addresses the question of whether ligand targeting of bubbles with abciximab improves the effectiveness of lysis with ultrasound. A partial thrombotic occlusion of the right common carotid artery of 16 rats was produced by insertion of human clot material via an external carotid artery catheter. Rats received abciximab immunobubbles, non-specific control immunobubbles or saline intravenously over 30 minutes in combination with pulsed 2 MHz ultrasound. Blood samples were taken at baseline and 5, 10, 20, 30 and 60 minutes after beginning treatment. Human D-dimer levels for quantification of thrombolysis were analysed by ELISA. Only animals treated with abciximab immunobubbles and ultrasound showed a significant increase of D-dimer levels over time (p = 0.043, linear trend p = 0.037), whereas in the other two groups, no significant increase over time was found. Overall, animals in the abciximab immunobubbles group showed higher plasma D-dimer levels than animals treated with non-specific immunobubbles (p = 0.049) and animals treated with ultrasound alone (p = 0.017). In histological sections, thrombi treated with abciximab immunobubbles and ultrasound showed clear signs of disintegration in contrast to thrombi in both control groups. 2 MHz ultrasound in combination with abciximab immunobubbles induces thrombolysis without lytic agents that is superior to insonation of non-specific immunobubbles.
Department of Neurology, University Hospital of Mannheim, Germany.
Angelika
A
Alonso
Carl-Erik
CE
Dempfle
Alberto
A
Della Martina
Mark
M
Stroick
Marc
M
Fatar
Katrin
K
Zohsel
Eric
E
Allémann
Michael G
MG
Hennerici
Stephen
S
Meairs
D000077284:Abciximab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D045423:Microbubbles; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D014465:Ultrasonics
D000911:Antibodies, Monoclonal; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; C036309:fibrin fragment D; D000077284:Abciximab