Development of a 64Cu-labeled CD4+ T cell targeting PET tracer: evaluation of CD4 specificity and its potential use in collagen-induced arthritis

Background CD4 + T cells are central inflammatory mediators in the pathogenesis of autoimmune rheumatoid arthritis (RA), as they are one of the dominating cell types in synovial inflammation. Molecular imaging of CD4 + T cells has potential role for early detection and monitoring of RA. Here, we dev...

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Published in:EJNMMI research 2022-09, Vol.12 (1), p.62-62, Article 62
Main Authors: Clausen, Anne Skovsbo, Christensen, Camilla, Christensen, Esben, Cold, Sigrid, Kristensen, Lotte Kellemann, Hansen, Anders Elias, Kjaer, Andreas
Format: Article
Language:English
Subjects:
[64Cu]Cu-NOTA-CD4
Accumulation
Animal model
Antibodies
Arthritis
Cardiac Imaging
CD4+ T cells
Chelating agents
Collagen
Collagen-induced arthritis
Copper
Dexamethasone
Evaluation
Flow cytometry
Fragments
Imaging
Lymphocytes
Medicine
Medicine & Public Health
Nuclear Medicine
Oncology
Original Research
Orthopedics
Pathogenesis
Positron emission tomography (PET)
Radioactive tracers
Radiology
Rheumatoid arthritis
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Summary:Background CD4 + T cells are central inflammatory mediators in the pathogenesis of autoimmune rheumatoid arthritis (RA), as they are one of the dominating cell types in synovial inflammation. Molecular imaging of CD4 + T cells has potential role for early detection and monitoring of RA. Here, we developed a new radiotracer for in vivo immunoPET imaging of murine CD4 + T cells and tested it in the collagen-induced arthritis (CIA) mouse model of human RA. Results The tracer, [ 64 Cu]Cu-NOTA-CD4-F(ab)’2 ([ 64 Cu]Cu-NOTA-CD4), was generated from F(ab)’2 fragments of R-anti-mouse CD4 antibodies conjugated to the 2- S -(isothiocyanatbenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid ( p -SCN-Bn-NOTA) chelator and radiolabeled with copper-64. Accumulation of the tracer and isotype control was evaluated in the CIA model and mice receiving whole-body irradiation (WBI) (5 Gy). The potential of [ 64 Cu]Cu-NOTA-CD4 for response assessment was evaluated in CIA induced mice treated with dexamethasone (DXM). Imaging data were compared with flow cytometry and immunohistochemistry (IHC) of inflammatory cells including CD4 + T cells. [ 64 Cu]Cu-NOTA-CD4 showed increased accumulation in T cell-rich tissues compared with isotype control ( p  
ISSN:2191-219X
2191-219X
DOI:10.1186/s13550-022-00934-7