Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

BACKGROUND: Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A (131)I-labeled anti-PD-L1 monoclonal antibody tracer, (131)I-PD-L1-Mab, was developed to study the target ability of noninvasive Cerenkov luminescence imaging in colorectal cancer xenograft mice. METHOD: Anti-PD-L1 monoclonal antibody labeled with (131)I ((131)I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of (131)I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, Western blot analysis, and immunofluorescence staining. The clinical application value of (131)I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated. RESULTS: (131)I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069 × 10(-9) M. The competitive inhibition assay further confirmed the specific binding ability of (131)I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer (131)I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% IA/g at 48 h. CONCLUSIONS: There is a great potential for (131)I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.