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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 < 0.0001). In addition, reduced accumulation of [ 64 Cu]Cu-NOTA-CD4 was observed in T cell-depleted tissue ( p < 0.0001). Flow cytometry and IHC confirmed the increased infiltration of CD4 + T cells in CIA mice. Conclusions We developed and evaluated a new radiotracer, [ 64 Cu]Cu-NOTA-CD4, for immunoPET imaging of murine CD4 + T cells. [ 64 Cu]Cu-NOTA-CD4 was successfully synthesized by F(ab)’2 fragments of R-anti-mouse CD4 antibodies conjugated to a chelator and radiolabeled with copper-64. We found that our novel CD4 PET tracer can be used for noninvasive visualization of murine CD4 + T cells. Supplementary Information The online version contains supplementary material available at 10.1186/s13550-022-00934-7.