Assessment of CCR2 PET for head and neck squamous cell carcinoma prognosis

Introduction: Despite advances in prevention and treatment, head and neck squamous cell carcinoma (HNSCC) represents a major cause of cancer-related mortality worldwide. Among newly diagnosed patients, two-thirds present with advanced disease involving regional lymph node metastases, leading to poor overall survival. Currently, identifying which patients will have favorable or unfavorable outcomes a priori has proven difficult, with no reliable method to stratify patients. Thus, there is an urgent need for clinically translatable molecular biomarkers to inform patient-specific management of HNSCC. Given the important role of chemokine receptor type 2 (CCR2) in HNSCC progression and metastasis, the goal of this study is to assess the potential of a CCR2 targeted PET tracer for HNSCC patient prognosis.

Methods: The novel CCR2-targerted PET tracer, ⁶⁴Cu-DOTA-ECL1i, was employed for HNSCC patient imaging. Dynamic (0-60 min) PET/CT scans were performed following intravenous administration, as well as a static scan between 1 h and 3 h post tracer injection. Six HNSCC patients were enrolled in the study between 2020 and 2021. The primary tumors and lymph node metastases from these patients were collected for histopathological characterization. The tracer binding to these cancerous tissues was further confirmed by ex vivo autoradiography. Blood samples from these patients were also collected at the end of dynamic scan for metabolite analysis.

Results: All six HNSCC patients demonstrated significant uptake in primary tumors (SUV_max= 3.2±0.7, n=6) and metastatic lymph nodes (SUV_max= 3.6±0.4, n=4) during the dynamic scans. Later static scans showed comparable uptake in these lesions (tumors= 2.7±0.7, n=6; lymph nodes= 3.1±1.1, n=6), indicating the stable binding and accumulation of ⁶⁴Cu-DOTA-ECL1i. Immunostaining of collected tumors and lymph nodes showed overexpression of CCR2 receptor in both squamous cells and CD68+ macrophages. Ex vivo autoradiography demonstrated specific binding of CCR2 tracer to cancerous tissues and correlation with CCR2 immunostaining. In contrast to clinical ¹⁸F-FDG PET, ⁶⁴Cu-DOTA-ECL1i showed uptake in close proximity to ¹⁸F-FDG signals but in a different profile.

Conclusions: The CCR2 targeting radiotracer ⁶⁴Cu-DOTA-ECL1i showed specific detection of both primary tumors and lymph node metastases in HNSCC patients. Ex vivo tissue characterization confirmed the tumor imaging specificity. Further studies are warranted to assess the potential of CCR2 PET for HNSCC prognosis.

• Download figure
• Open in new tab
• Download powerpoint