Head-to-Head Comparison of [68 Ga]Ga-FAPI-46-PET/CT and [18F]F-FDG-PET/CT for Radiotherapy Planning in Head and Neck Cancer

Introduction In head and neck cancers (HNCs), fibroblast activation protein (FAP) is expressed by cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Preliminary evidence suggests that detection and staging is feasible with positron emission tomography (PET/CT) imaging using [ 68 Ga]-radiolabeled inhibitors of FAP ([ 68 Ga]Ga-FAPI-46) in HNCs. This study aims to compare [ 68 Ga]Ga-FAPI-46 PET/CT and [ 18 F]-fluorodeoxy- d -glucose ([ 18 F]F-FDG) PET/CT with a focus on improved target volume definition and radiotherapy planning in patients with HNC referred for chemoradiation. Methods A total of 15 patients with HNCs received both [ 68 Ga]Ga-FAPI-46 PET/CT and [ 18 F]F-FDG PET/CT with a thermoplastic mask, in addition to initial tumor staging by conventional imaging with contrast-enhanced CT and/or MRI. Mean intervals between FAPI/FDG and FAPI/conventional imaging were 4 ± 20 and 17 ± 18 days, respectively. Location and number of suspicious lesions revealed by the different procedures were recorded. Subsequently, expert-generated gross tumor volumes (GTVs) based on conventional imaging were compared to those based on [ 18 F]F-FDG and [ 68 Ga]Ga-FAPI-46 PET/CT to measure the impact on subsequent radiation planning. Results All patients had focal FAPI uptake above background in tumor lesions. Compared to FDG, tumor uptake (median SUVmax 10.2 vs. 7.3, p = 0.008) and tumor-to-background ratios were significantly higher with FAPI than with FDG (SUVmean liver: 9.3 vs. 3.2, p