Targeted Radionuclide Therapy With ¹³¹I-Labeled Anti-PD-L1 Antibody Suppresses Pharyngeal Squamous Cell Carcinoma in the Animal Model.

Abstract

Pharyngeal squamous cell carcinoma (PSCC) is an aggressive subtype of head and neck squamous cell carcinoma (HNSCC) with poor prognosis and low survival rates. Immune checkpoint inhibitors (ICIs) show promise, but less than 20% of HNSCC patients respond positively. Targeted radionuclide therapy (TRT) combines radionuclides with monoclonal antibodies to target tumor cells. This study created a reliable animal model of PSCC for evaluating the therapeutic efficacy of ¹³¹I-aPD-L1. Nude mice were subcutaneously implanted with FaDu cells-a human PSCC cell line characterized by high PD-L1 expression. The synthesis of ¹³¹I-aPD-L1 was optimized by varying labeling conditions, achieving a labeling efficiency of over 90%. Mice were divided into experimental and control groups; the experimental group received a single intravenous injection of 500 μCi ¹³¹I-aPD-L1. Accumulation of ¹³¹I-aPD-L1 in tumor tissues was confirmed by animal single-photon emission computed tomography (SPECT). Tumor volume and mouse body weight were measured every 3 days for 30 days. At the end of the study, tumor tissues were stained for histological examination and immunohistochemical analysis of Bcl-2 and Caspase-3 expression levels. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was also performed on tumor tissues. SPECT verified a significant accumulation of ¹³¹I in FaDu tumor tissue. The experimental group exhibited significantly slower tumor volume increase compared to the control group (t = 2.37, p < 0.05). Additionally, a significant reduction in body weight was observed in the ¹³¹I-aPD-L1 group compared to the control group (t = 5.624, p < 0.01). HE staining showed extensive tumor necrosis in the experimental group. Immunohistochemical analysis revealed negative Bcl-2 expression and higher caspase-3 expression in the experimental group, indicating enhanced apoptosis and necrosis in tumor cells. Furthermore, TUNEL assay further confirmed that ¹³¹I exerted cytotoxic effects by inducing DNA fragmentation. Collectively, our findings demonstrate the promising therapeutic potential of ¹³¹I-aPD-L1 for PSCC, particularly in patients with drug resistance or recurrent head and neck tumors. However, the use of nude mice may have impacted the full therapeutic efficacy and synergistic potential observed with immunotherapy. Future studies should utilize immunocompetent models to better assess the probe's therapeutic impact and to explore its synergistic effects with immunotherapy and reduce the dose of ¹³¹I to mitigate its toxic effects.