The Added Value of<sup>68</sup>Ga-FAPI PET/CT in Patients with Head and Neck Cancer of Unknown Primary with<sup>18</sup>F-FDG–Negative Findings
Bingxin Gu, Xiaoping Xu, Ji Zhang, Xiaomin Ou, Zuguang Xia, Qing Guan, Silong Hu, Zhongyi Yang, Shaoli Song
Abstract
<sup>18</sup>F-fluorodeoxyglucose (<sup>18</sup>F-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 <sup>18</sup>F-FDG-PET/CT scan in some cases. As <sup>68</sup>Ga-radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT has promising results in detecting different tumor entities, our study aimed to evaluate the performance of <sup>68</sup>Ga-FAPI-PET/CT for detecting the primary tumor in HNCUP patients with negative <sup>18</sup>F-FDG findings. <b>Methods:</b> A total of eighteen patients (16 males and 2 females; median age, 55 years; range, 24-72 years) with negative <sup>18</sup>F-FDG findings were enrolled in this study. All patients underwent <sup>18</sup>F-FDG and <sup>68</sup>Ga-FAPI-PET/CT within one week. Biopsy and histopathological examinations were done in the sites with positive <sup>68</sup>Ga-FAPI-PET/CT findings. <b>Results:</b><sup>68</sup>Ga-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<sub>max</sub>, 8.79; range, 2.60-16.50) and excellent tumor-to-contralateral normal tissue ratio (mean SUV<sub>max</sub> 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<sub>max</sub> of lymph node metastases were 9.05 ± 5.29 for FDG and 9.08 ± 4.69 for FAPI (<i>P</i> = 0.975); as for bone metastases, the mean SUV<sub>max</sub> were 8.11 ± 3.00 for FDG and 6.96 ± 5.87 for FAPI, respectively (<i>P</i> = 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 (<i>P</i> = 0.100) and 9.08 ± 3.35 vs. 9.14 ± 8.40 (<i>P</i> = 0.976), respectively. <b>Conclusion:</b> We presented first evidence of diagnostic role of <sup>68</sup>Ga-FAPI-PET/CT in HNCUP, and our study demonstrated that <sup>68</sup>Ga-FAPI-PET/CT had the potential to improve the detection rate of primary tumor in HNCUP patients with negative FDG findings. Moreover, <sup>68</sup>Ga-FAPI had similar performance in assessing metastases with <sup>18</sup>F-FDG.