Preliminary Research of Radiolabeled Atezolizumab for the Noninvasive Evaluation of TNBC PD‐L1 Expression In Vivo

ABSTRACT Programmed death‐ligand 1 (PD‐L1) expression is related to the efficacy and prognosis in triple‐negative breast cancer. This study employed an indirect labeling method to synthesize [ 125 I]PI‐Atezolizumab. The in vitro stability of [ 125 I]PI‐Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [ 125 I]PI‐Atezolizumab to MDA‐MB‐231 cells expressing humanized PD‐L1 was assessed through in vitro incubation, yielding a K d value comparable to that of Atezolizumab. This suggests that the labeling process did not compromise the affinity of the Atezolizumab to PD‐L1. Subsequently, pharmacokinetic studies were conducted in normal mice and biodistribution experiments in tumor‐bearing mice. A comparison of the biodistribution results between [ 125 I]PI‐Atezolizumab and 125 I‐labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [ 125 I]PI‐Atezolizumab for PD‐L1 in MDA‐MB‐231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [ 125 I]PI‐Atezolizumab, prepared via indirect labeling, for monitoring PD‐L1 in triple‐negative breast cancer models.