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RESEARCH Open Access© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modif i ed the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit h t t p : / / c r e a t i v e c o m m o n s . o r g / l i c e n s e s / b y - n c - n d / 4 . 0 /.Duan et al. Journal of Translational Medicine (2025) 23:150 https://doi.org/10.1186/s12967-024-05899-wJournal of Translational Medicine† Shao Duan and Chao Li are co-f i rst authors.*Correspondence:Weiyu Chenweiyuchen@zju.edu.cnZunyu Xiaofyyxiaozunyu@nbu.edu.cnGongping Xu13704846805@163.comFull list of author information is available at the end of the articleAbstractBackground Activated T cells play a pivotal role in rheumatoid arthritis (RA) pathogenesis, and imaging of activated T cells may provide a non-invasive tool for RA detection. Here, we fi rst developed an optical probe targeting human inducible T cell co-stimulator (ICOS) and tested its capacity in RA diagnosis by capturing ICOS + activated T cells in vivo in a humanized mouse model.Methods The humanized arthritis model, Human peripheral blood mononuclear cells- adjuvant induced arthritis (HuPBMC-AIA) was established, and fl ow cytometry and immunof l uorescence were employed to determine ICOS expression in huPBMC-AIA model. Anti-human ICOS monoclonal antibody (mAb) was conjugated to Cy7 via NHS ester amine reaction. A cell uptake study was used to conf i rm the specif i city of Cy7-ICOS mAb to activated T cells. 4-view near-infrared fl uorescence (NIRF) imaging study was performed to test Cy7-ICOS mAb in detecting RA in vivo.Findings ICOS was conf i rmed as an indicator of RA pathogenesis via RNA-seq, fl ow cytometry and immunof l uorescence data. An in-vitro cellular uptake study validated the specif i city of Cy7-ICOS mAb to activated T cells. Cy7-ICOS mAb could detect ICOS + activated T cells in vivo through 4-view NIRF imaging. The receiver operating characteristic (ROC) curve created based on NIRF imaging quantif i cation could distinguish the huPBMC-AIA group from the control group at all time points imaged.Conclusion In this study, we fi rst developed an optical imaging probe targeting human ICOS, Cy7-ICOS mAb. The 4-view NIRF imaging with Cy7-ICOS mAb could detect pathogenic ICOS + activated T cells with high sensitivity and specif i city in vivo, which indicated the great potential of this imaging probe in RA early diagnosis.Non-invasive imaging with ICOS-targeting monoclonal antibody for preclinical diagnosis of rheumatoid arthritis in a humanized mouse modelShao Duan 1† , Chao Li 1† , Feng Yan 2 , Yifei Xia 1 , Shuaiming Shao 2 , Weiyu Chen 3,4* , Zunyu Xiao 5* and Gongping Xu 1*