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
Simone Wegen, Lutz van Heek, Philipp Linde, Karina Claus, Dennis Akuamoa-Boateng, Christian Baues, Shachi Jenny Sharma, Klaus Schomäcker, Thomas Fischer, Katrin Sabine Roth, Jens Peter Klußmann, Simone Marnitz, Alexander Drzezga, Carsten Kobe
Abstract
Abstract 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 < 0.001; SUVmean bloodpool: 6.9 vs. 4.0, p < 0.001). A total of 49 lesions were recorded. Of these, 40 (82%) were FDG + and 41 (84%) were FAP + . There were 5 (10%) FAP + /FDG − lesions and 4 (8%) FAP − /FDG + lesions. Volumetrically, a significant difference was found between the GTVs (median 57.9 ml in the FAPI-GTV, 42.5 ml in the FDG-GTV, compared to 39.2 ml in the conventional-GTV). Disease stage identified by FAPI PET/CT was mostly concordant with FDG PET/CT. Compared to conventional imaging, five patients (33%) were upstaged following imaging with FAPI and FDG PET/CT. Conclusion We demonstrate that [ 68 Ga]Ga-FAPI-46 -PET/CT is useful for detecting tumor lesions in patients with HNCs. There is now a need for prospective randomized studies to confirm the role of [ 68 Ga]Ga-FAPI-46 PET/CT in relation to [ 18 F]F-FDG PET/CT in HNCs and to evaluate its impact on clinical outcome.