[18F]F FDG PET/CT and [68Ga]Ga-FAPI-4 PET/CT Imaging Following EGFR Targeted Erlotinib Treatment Toward Accurate Disease Status Evaluation in Metastatic or Advanced Head and Neck squamous Cell Carcinoma (HNSCC): A Complementary Role?

Abstract Head and neck squamous cell carcinoma (HNSCC) comprises a heterogeneous group of malignancies affecting the oral cavity, pharynx, and larynx, representing the seventh most common malignancy worldwide. Management of HNSCC with standard treatments remains inadequate in a substantial fraction of patients. Epidermal growth factor receptor (EGFR) is a novel treatment target, which is overexpressed in approximately 90% of HNSCC, making EGFR inhibitors such as erlotinib a promising therapeutic agent. [18F]F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) serves as the standard imaging modality for HNSCC management, while [68Ga]Ga-fibroblast activation protein inhibitor-04 (FAPI-04) represents an emerging radiotracer showing superior performance in specific clinical scenarios. We herein present two HNSCC patients who underwent two imaging modalities ([18F]F-FDG PET/CT and [68Ga]Ga-FAPI-04 PET/CT) following erlotinib treatment. In the first patient, [18F]F-FDG-PET/CT failed to identify metastatic cervical and mediastinal lymph nodes and skeletal lesions that were clearly visualized on [68Ga]Ga-FAPI-04 PET/CT. In patient 2, post-erlotinib, [68Ga]Ga-FAPI-04 PET/CT demonstrated reduced uptake in primary and lymph nodal lesions compared to [18F]F-FDG PET/CT. These findings suggest that both molecular imaging agents provide complementary information for accurate disease status evaluation and treatment response assessment in advanced HNSCC patients receiving erlotinib therapy.