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

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 [¹²⁵I]PI-Atezolizumab. The in vitro stability of [¹²⁵I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [¹²⁵I]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 [¹²⁵I]PI-Atezolizumab and ¹²⁵I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [¹²⁵I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [¹²⁵I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.