Value of [18F]AlF-NOTA-FAPI PET/CT in guiding radiotherapy planning for stage I-IIIC lung cancer: A comparison with contrast-enhanced CT and [18F]FDG PET/CT

Abstract Purpose To evaluate the usefulness of [ 18 F]AlF-labeled fibroblast activation protein inhibitor (FAPI), chelated with NOTA (denoted as [ 18 F]AlF-NOTA-FAPI), positron emission tomography/computed tomography (PET/CT) for radiotherapy planning in lung cancer, we compared it with contrast-enhanced CT (CE-CT) and [ 18 F]FDG PET/CT. Materials and methods In this secondary analysis of a prospective trial, patients with stage I-III lung cancer who underwent [ 18 F]AlF-NOTA-FAPI and CE-CT or [ 18 F]FDG PET/CT scans within 2 weeks were selected. Gross tumor volume (GTV), clinical tumor volume (CTV), and planning tumor volume (PTV) were drawn for the primary tumor (GTVp) and involved lymph nodes (GTVnd) based on CE-CT, [ 18 F]AlF-NOTA-FAPI PET/CT and [ 18 F]FDG PET/CT. Organs at risk were evaluated and compared in intensity-modulated radiation therapy (IMRT) and intensity-modulated proton therapy (IMPT) plans. Results Fifty-one patients (median age, 64 years; 38 males [74.5%]) were evaluated. Statistically significant differences in GTVs based on CE-CT, [ 18 F]AlF-NOTA-FAPI PET/CT, and [ 18 F]FDG PET/CT were found between each pair (all P < 0.05), except that no difference in GTVp was found between [ 18 F]AlF-NOTA-FAPI and [ 18 F]FDG PET/CT ( P = 0.558). CE-CT-based GTVp values were significantly larger than those based on [ 18 F]FDG PET/CT and [ 18 F]AlF-NOTA-FAPI PET/CT due to the presence of obstructive pneumonia ( n = 18; all P < 0.05). PTVall-IMRT based on CE-CT (351.98 ± 26.87) was significantly larger than that based on [ 18 F]AlF-NOTA-FAPI PET/CT (329.98 ± 26.21; P = 0.03). PTVall-IMPT based on CE-CT (212.74 ± 18.73) was significantly larger than those based on [ 18 F]FDG PET/CT (204.26 ± 19.34) and [ 18 F]AlF-NOTA-FAPI PET/CT (196.99 ± 18.38), with P -values of 0.046 and 0.011, respectively. For IMRT, [ 18 F]AlF-NOTA-FAPI PET/CT-based plans significantly reduced the radiation doses received by the heart, contralateral lung, and both lungs (all P < 0.05). Conclusion [ 18 F]AlF-NOTA-FAPI PET/CT shows promise as a valuable tool for radiotherapy planning in lung cancer, providing accurate target delineation and improved sparing of critical organs. Trial registration This study was approved by the Clinical Research Ethics Committee of our institution.