The Added Value of ⁶⁸Ga-FAPI-04 PET/CT in Patients with Head and Neck Cancer of Unknown Primary with ¹⁸F-FDG Negative Findings

Abstract

¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in locating of primary tumor for patients with head and neck cancer of unknown primary (HNCUP). Nevertheless, it can be challenging to locate the primary malignancy in ¹⁸F-FDG-PET/CT scan in some cases. As ⁶⁸Ga-radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT has promising results in detecting different tumor entities, our study aimed to evaluate the performance of ⁶⁸Ga-FAPI-PET/CT for detecting the primary tumor in HNCUP patients with negative ¹⁸F-FDG findings. Methods: A total of eighteen patients (16 males and 2 females; median age, 55 years; range, 24-72 years) with negative ¹⁸F-FDG findings were enrolled in this study. All patients underwent ¹⁸F-FDG and ⁶⁸Ga-FAPI-PET/CT within one week. Biopsy and histopathological examinations were done in the sites with positive ⁶⁸Ga-FAPI-PET/CT findings. Results: ⁶⁸Ga-FAPI-PET/CT detected the primary tumor in 7 out of 18 patients (38.89%). Among the 7 patients, in respect of the primary tumor sites, 1 was in nasopharynx, 2 were in palatine tonsil, 2 were in submandibular gland, and 2 were in hypopharynx. The primary tumors showed moderate to intensive uptake of FAPI (mean SUV_max, 8.79; range, 2.60-16.50) and excellent tumor-to-contralateral normal tissue ratio (mean SUV_max ratio, 4.50; range, 2.17-8.21). In lesion-based analysis, a total of 65 lymph nodes and 17 bone metastatic lesions were identified. The mean SUV_max of lymph node metastases were 9.05 ± 5.29 for FDG and 9.08 ± 4.69 for FAPI (P = 0.975); as for bone metastases, the mean SUV_max were 8.11 ± 3.00 for FDG and 6.96 ± 5.87 for FAPI, respectively (P = 0.478). The mean tumor-to-background ratio (TBR) values of lymph node and bone metastases were 10.65 ± 6.59 vs. 12.80 ± 8.11 (P = 0.100) and 9.08 ± 3.35 vs. 9.14 ± 8.40 (P = 0.976), respectively. Conclusion: We presented first evidence of diagnostic role of ⁶⁸Ga-FAPI-PET/CT in HNCUP, and our study demonstrated that ⁶⁸Ga-FAPI-PET/CT had the potential to improve the detection rate of primary tumor in HNCUP patients with negative FDG findings. Moreover, ⁶⁸Ga-FAPI had similar performance in assessing metastases with ¹⁸F-FDG.