Detection of activated platelets in a mouse model of carotid artery thrombosis with 18F-labeled single-chain antibodies |
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| Institution: | 1. Vascular Biotechnology Laboratory, Baker IDI, Melbourne, Australia;2. Atherothrombosis and Vascular Biology Laboratory, Baker IDI, Melbourne, Australia;3. Departments of Nuclear Medicine and Centre for PET, Austin Hospital, Melbourne, Australia;4. Department of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia;5. Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia;6. The Florey Institute of Neuroscience and Mental Health, Austin Hospital, Melbourne, Australia;7. Central Clinical School, Monash University, Melbourne, Australia;1. Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Germany;2. Institut für Pharmakologie und Toxikologie, Universitätsklinikum Bonn, Germany;3. Kardiologische Abteilung, Innere Medizin, Isarklinik München, Germany;1. Molecular Imaging and Radiochemistry, Nuclear Medicine Clinic, Friedrich-Alexander University, Schwabachanlage 6, D-91054 Erlangen, Germany;2. Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany;1. IIS-Fundacion Jimenez Diaz-Autonoma University, Madrid, Spain;2. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain |
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| Abstract: | IntroductionActivated 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 18F PET radiotracer based on this antibody.MethodsScFvanti-LIBS and control antibody mut-scFv were reacted with N-succinimidyl-4-18F]fluorobenzoate (S18F]FB). Radiolabeled scFv was incubated with in vitro formed platelet clots and injected into mice with FeCl3 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.ResultsAfter incubation with increasing concentrations of 18F-scFvanti-LIBS clots had retained significantly higher amounts of radioactivity compared to clots incubated with radiolabeled 18F-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).ConclusionsOur results show that the novel antibody radiotracer 18F-scFvanti-LIBS is useful for the sensitive detection of activated platelets and thrombosis.Advances in knowledge and implications for patient careWe describe the first 18F variant of a scFvanti-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. |
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