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Title: Detection of activated platelets in a mouse model of carotid artery thrombosis with 18 F-labeled single-chain antibodies.
Austin Authors: Ardipradja, Katie;Yeoh, Shinn Dee;Alt, Karen;O'Keefe, Graeme J;Rigopoulos, Angela;Howells, David William;Scott, Andrew M ;Peter, Karlheinz;Ackerman, Uwe;Hagemeyer, Christoph E
Affiliation: Atherothrombosis and Vascular Biology Laboratory, Baker IDI, Melbourne, Australia
Vascular Biotechnology Laboratory, Baker IDI, Melbourne, Australia
Central Clinical School, Monash University, Melbourne, Australia
Department of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
Departments of Nuclear Medicine and Centre for PET, Austin Hospital, Melbourne, Australia
The Florey Institute of Neuroscience and Mental Health, Austin Hospital, Melbourne, Australia
Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia
Issue Date: 18-Dec-2013
Publication information: Nuclear Medicine and Biology 2013; 41(3): 229-37
Abstract: Activated platelets are key players in thrombosis and inflammation. We previously generated single-chain antibodies (scFv) against ligand-induced binding sites (LIBS) on the highly abundant platelet glycoprotein integrin receptor IIb/IIIa. The aim of this study was the construction and characterisation of a novel (18)F PET radiotracer based on this antibody.ScFv(anti-LIBS) and control antibody mut-scFv were reacted with N-succinimidyl-4-[(18)F]fluorobenzoate (S[(18)F]FB). Radiolabeled scFv was incubated with in vitro formed platelet clots and injected into mice with FeCl(3) induced thrombus in the left carotid artery. Clots were imaged in the PET scanner and amount of radioactivity measured using an ionization chamber and image analysis. Assessment of vessel injury as well as the biodistribution of the radiolabeled scFv was studied.After incubation with increasing concentrations of (18)F-scFv(anti-LIBS) clots had retained significantly higher amounts of radioactivity compared to clots incubated with radiolabeled (18)F-mut-scFv (13.3 ± 3.8 vs. 3.6 ± 1 KBq, p < 0.05, n = 9, decay corrected). In the in vivo experiments we found an high uptake of the tracer in the injured vessel compared with the non-injured vessel, with 12.6 ± 4.7% injected dose per gram (ID/g) uptake in the injured vessel and 3.7 ± 0.9% ID/g in the non-injured vessel 5 minutes after injection (p < 0.05, n = 6).Our results show that the novel antibody radiotracer (18)F-scFv(anti-LIBS) is useful for the sensitive detection of activated platelets and thrombosis.We describe the first (18)F variant of a scFv(anti-LIBS) against activated platelets. This diagnostic agent could provide a powerful tool for the assessment of acute thrombosis and inflammation in patients in the future.
Gov't Doc #: 24440583
DOI: 10.1016/j.nucmedbio.2013.12.006
Journal: Nuclear medicine and biology
Type: Journal Article
Subjects: Antibodies
Blood Coagulation
Carotid Artery Thrombosis.pathology.physiopathology.radionuclide imaging
Disease Models, Animal
Fluorine Radioisotopes.diagnostic use
Image Processing, Computer-Assisted
Mice, Inbred C57BL
Platelet Activation
Positron-Emission Tomography
Single-Chain Antibodies.chemistry.diagnostic use.pharmacokinetics
Appears in Collections:Journal articles

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