Assessment of CCR2 PET as a Biomarker for Head and Neck Squamous Cell Carcinoma

Because of the lack of prognostic biomarkers, most patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed at an advanced stage of the disease, leading to poor overall survival. There is an unmet need to identify biomarkers for the assessment of HNSCC. The goal of this study was to assess C-C chemokine receptor type 2 (CCR2) as a new diagnostic biomarker for HNSCC. Methods: The sensitivity and specificity of the CCR2-targeting radiotracer ⁶⁴Cu-DOTA-ECL1i for tumor detection was assessed in a mouse oral carcinoma 1 (MOC1) xenograft model and compared with ¹⁸F-FDG. The capability of ⁶⁴Cu-DOTA-ECL1i for monitoring MOC1 tumor treatment response was evaluated for multiple treatment strategies. The CCR2 inhibitor propagermanium was used for targeted therapy in the MOC1 tumor model, followed by ⁶⁴Cu-DOTA-ECL1i imaging. The translational potential of ⁶⁴Cu-DOTA-ECL1i for HNSCC imaging was further investigated using patient-derived xenograft models. Proof-of-concept studies were performed using primary tumors and lymph node metastases of 11 patients with HNSCC. Histopathologic analyses of tumors in mice and humans were performed to characterize the expression of CCR2 and associated cell types. Results: ⁶⁴Cu-DOTA-ECL1i PET imaged MOC1 tumors with high contrast, tracked the increase of tumor volume, and monitored the treatment responses. Propagermanium effectively inhibited MOC1 tumor growth and significantly improved survival. In the patient-derived xenograft model, ⁶⁴Cu-DOTA-ECL1i accurately identified the tumors and sensitively tracked their progression. In patients with HNSCC, CCR2 PET revealed strong and heterogeneous uptake within primary tumors and metastatic lymph nodes. Tissue analyses demonstrated overexpression of CCR2 on both tumor cells and macrophages. Conclusion: ⁶⁴Cu-DOTA-ECL1i PET accurately detected the expression of CCR2 in patients with HNSCC. The effectiveness of propagermanium in the inhibition of MOC1 tumor progression indicated its potential for HNSCC therapy.