TY - JOUR
T1 - Imaging CD19+ B Cells in an Experimental Autoimmune Encephalomyelitis Mouse Model using Positron Emission Tomography
AU - Reyes, Samantha T.
AU - Azevedo, E. Carmen
AU - Cropper, Haley C.
AU - Nagy, Sydney
AU - Deal, Emily M.
AU - Chaney, Aisling M.
AU - James, Michelle L.
N1 - Funding Information:
We are grateful for the support from the SCi3 small-animal imaging facility at Stanford and Dr. Frezghi Habte for his technical assistance with the PET/CT. LC-MS is performed by the core staff at the Stanford University Mass Spectrometry (SUMS) core facility and we appreciate the staff for providing this service. We thank Horizon Therapeutics for very kindly providing the hCD19-mAb and Jodi Karnell in particular for her technical guidance and support. This work was funded by the NIH NINDS (1 R01 NS114220-01A1).
Publisher Copyright:
© 2023 JoVE Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.
PY - 2023/1
Y1 - 2023/1
N2 - Multiple sclerosis (MS) is the most common demyelinating central nervous system (CNS) disease affecting young adults, often resulting in neurological deficits and disability as the disease progresses. B lymphocytes play a complex and critical role in MS pathology and are the target of several therapeutics in clinical trials. Currently, there is no way to accurately select patients for specific anti-B cell therapies or to non-invasively quantify the effects of these treatments on B cell load in the CNS and peripheral organs. Positron emission tomography (PET) imaging has enormous potential to provide highly specific, quantitative information regarding the in vivo spatiotemporal distribution and burden of B cells in living subjects. This paper reports methods to synthesize and employ a PET tracer specific for human CD19+ B cells in a well-established B cell-driven mouse model of MS, experimental autoimmune encephalomyelitis (EAE), which is induced with human recombinant myelin oligodendrocyte glycoprotein 1-125. Described here are optimized techniques to detect and quantify CD19+ B cells in the brain and spinal cord using in vivo PET imaging. Additionally, this paper reports streamlined methods for ex vivo gamma counting of disease-relevant organs, including bone marrow, spinal cord, and spleen, together with high-resolution autoradiography of CD19 tracer binding in CNS tissues.
AB - Multiple sclerosis (MS) is the most common demyelinating central nervous system (CNS) disease affecting young adults, often resulting in neurological deficits and disability as the disease progresses. B lymphocytes play a complex and critical role in MS pathology and are the target of several therapeutics in clinical trials. Currently, there is no way to accurately select patients for specific anti-B cell therapies or to non-invasively quantify the effects of these treatments on B cell load in the CNS and peripheral organs. Positron emission tomography (PET) imaging has enormous potential to provide highly specific, quantitative information regarding the in vivo spatiotemporal distribution and burden of B cells in living subjects. This paper reports methods to synthesize and employ a PET tracer specific for human CD19+ B cells in a well-established B cell-driven mouse model of MS, experimental autoimmune encephalomyelitis (EAE), which is induced with human recombinant myelin oligodendrocyte glycoprotein 1-125. Described here are optimized techniques to detect and quantify CD19+ B cells in the brain and spinal cord using in vivo PET imaging. Additionally, this paper reports streamlined methods for ex vivo gamma counting of disease-relevant organs, including bone marrow, spinal cord, and spleen, together with high-resolution autoradiography of CD19 tracer binding in CNS tissues.
UR - http://www.scopus.com/inward/record.url?scp=85147390981&partnerID=8YFLogxK
U2 - 10.3791/64133
DO - 10.3791/64133
M3 - Article
C2 - 36744792
AN - SCOPUS:85147390981
SN - 1940-087X
VL - 2023
JO - Journal of Visualized Experiments
JF - Journal of Visualized Experiments
IS - 191
M1 - e64133
ER -