Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis
| Autor: | Marion S. Buckwalter, Michelle L. James, Isaac M. Jackson, Kendra J. Lechtenberg, Haley C. Cropper, Katherine L. Lucot, Aisling Chaney, Marc Y. Stevens |
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| Rok vydání: | 2020 |
| Předmět: |
Pathology
medicine.medical_specialty Encephalomyelitis Autoimmune Experimental medicine.drug_class Antigens CD19 Immunology Central nervous system Monoclonal antibody lcsh:RC346-429 Myelin oligodendrocyte glycoprotein Multiple sclerosis Mice Cellular and Molecular Neuroscience EAE mice medicine Animals Radioactive Tracers B cell lcsh:Neurology. Diseases of the nervous system B-Lymphocytes B cells biology CD19 business.industry Research General Neuroscience Experimental autoimmune encephalomyelitis Brain medicine.disease Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure PET Spinal Cord Neurology Positron-Emission Tomography biology.protein Female business Ex vivo Immunostaining |
| Zdroj: | Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-11 (2020) Journal of Neuroinflammation |
| Popis: | Background B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1–125). PET imaging of naïve and EAE mice was performed 19 h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted. Results Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/μmol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry—providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice. Conclusion CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS. |
| Databáze: | OpenAIRE |
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