Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis
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(2020) 17:275
RESEARCH
Open Access
Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis Marc Y. Stevens1† , Haley C. Cropper1† , Katherine L. Lucot2, Aisling M. Chaney1, Kendra J. Lechtenberg3, Isaac M. Jackson1, Marion S. Buckwalter3 and Michelle L. James1,3*
Abstract 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. Keywords: PET, Multiple sclerosis, EAE mice, B cells, CD19
* Correspondence: [email protected] † Marc Y. Stevens and Haley C. Cropper contributed equally to this work. 1 Department of Radiology, Molecular Imaging Program at Stanford, 1201 Welch Rd, Stanford, CA 94305, USA 3 Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the sou
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