RT Journal Article SR Electronic T1 Imaging of Tumor Stroma Using 68Ga-FAPI PET/CT to Improve Diagnostic Accuracy of Primary Tumors in Head and Neck Cancer of Unknown Primary: A Comparative Imaging Trial JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 365 OP 371 DO 10.2967/jnumed.123.266556 VO 65 IS 3 A1 Gu, Bingxin A1 Yang, Ziyi A1 Du, Xinyue A1 Xu, Xiaoping A1 Ou, Xiaomin A1 Xia, Zuguang A1 Guan, Qing A1 Hu, Silong A1 Yang, Zhongyi A1 Song, Shaoli YR 2024 UL http://jnm.snmjournals.org/content/65/3/365.abstract AB The low detection rate of primary tumors by current diagnostic techniques remains a major concern for patients with head and neck cancer of unknown primary (HNCUP). Therefore, in this study, we aimed to investigate the potential role of 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT compared with 18F-FDG PET/CT for the detection of primary tumors of HNCUP. Methods: In this prospective comparative imaging trial conducted at Fudan University Shanghai Cancer Center, 91 patients with negative or equivocal findings of a primary tumor by comprehensive clinical examination and conventional imaging were enrolled from June 2020 to September 2022. The presence of a primary tumor was recorded by 3 experienced nuclear medicine physicians. Primary lesions were validated by histopathologic analysis and a composite reference standard. Results: Of the 91 patients (18 women, 73 men; median age, 60 y; age range, 24–76 y), primary tumors were detected in 46 (51%) patients after a thorough diagnostic work-up. 68Ga-FAPI PET/CT detected more primary lesions than 18F-FDG PET/CT (46 vs. 17, P < 0.001) and showed better sensitivity, positive predictive value, and accuracy in locating primary tumors (51% vs. 25%, 98% vs. 43%, and 51% vs. 19%, respectively). Furthermore, 68Ga-FAPI PET/CT led to treatment changes in 22 of 91 (24%) patients compared with 18F-FDG PET/CT. The Kaplan–Meier curve illustrated that patients with unidentified primary tumors had a significantly worse prognosis than patients with identified primary tumors (hazard ratio, 5.77; 95% CI, 1.86–17.94; P = 0.0097). Conclusion: 68Ga-FAPI PET/CT outperforms 18F-FDG PET/CT in detecting primary lesions and could serve as a sensitive, reliable, and reproducible imaging modality for HNCUP patients.