Feasibility study of non-invasive evaluation of human PD-1 expression using 125I-nivolumab in a mouse tumor model

Abstract The immune checkpoint inhibitor, nivolumab, promotes robust antitumor efficacy in terms of blocking programmed cell death-1 (PD-1). The need is increasing to develop non-invasive imaging approach for evaluating human PD-1 (hPD-1) expression in tumors. The purpose of this study is to investigate whether we can evaluate the human PD-1 (hPD-1) expression non-invasively using 125I-nivolumab in a tumor model. Firstly, we confirmed the hPD-1 expression in Raji-hPD-1 cells by flow cytometry. In vitro cell binding assay for the determination of immunoreactivity showed specific binding of 125I-nivolumab to hPD-1 receptors of Raji cells and the dissociation constants (Kd) was 4.41 nM. Most importantly, single photon emission computed tomography/CT (SPECT/CT) images indicated that 125I-nivolumab uptake in Raji-hPD-1 tumor group showed higher than that of cold blocking group at 48 h and 168 h. In addition, we found that the signal intensity of hPD-1 expressing Raji tumor revealed 4.5-fold higher 125I-nivolumab uptake compared to Raji-null tumor (P<0.05) by autoradiography. Taken together, we established the labeling technique of 125I-nivolumab to evaluate the expression of human PD-1 non-invasively in a mouse tumor model. This technique might be developed further for the clinical application of non-invasive evaluation of hPD-1.