CD70-Targeted [18F]RCCB6 Immuno-PET/CT Imaging in Patients with Nasopharyngeal Carcinoma: A Proof-of-Concept Study

CD70 has emerged as a promising biomarker for nasopharyngeal carcinoma (NPC). This study investigated CD70 expression patterns in NPC specimens and evaluated the diagnostic potential of CD70-targeted [¹⁸F]RCCB6 immuno-PET/CT in patients with NPC. Methods: CD70 expression was analyzed in 80 archived NPC specimens and correlated with clinical and pathologic features. Using [¹⁸F]RCCB6, a single-domain antibody-derived tracer specific for human CD70, the diagnostic efficacy of [¹⁸F]RCCB6 immuno-PET/CT was assessed in 25 patients with NPC and compared with that of ¹⁸F-FDG PET/CT. Results: CD70 was positively expressed in 72 (90%) of 80 NPC specimens, with expression levels strongly correlated with Epstein-Barr virus (EBV) titers (r_s = 0.437; P < 0.001) and N-staging (P = 0.006). In all 15 patients with early-stage NPC, [¹⁸F]RCCB6 immuno-PET/CT achieved a 100% detection rate of the primary tumor and a 93% detection rate (75/81) of local lymph node metastasis. [¹⁸F]RCCB6 uptake correlated well with CD70 expression. In a head-to-head comparison, [¹⁸F]RCCB6 demonstrated higher sensitivity than did ¹⁸F-FDG in detecting lymph node metastasis (100% [58/58] vs. 90% [52/58], respectively; P = 0.031), and equivalent detection abilities for primary lesions and most distant metastases (100%). Notably, [¹⁸F]RCCB6 immuno-PET/CT demonstrated better evaluation of skull-base invasion with a clear border and bone metastases, as indicated by its higher uptake compared with ¹⁸F-FDG (7.25 vs. 5.95; P = 0.025). Conclusion: CD70 is a potent biomarker for NPC. [¹⁸F]RCCB6 immuno-PET/CT provides precise mapping of CD70 expression and enhances the diagnosis of primary, metastatic, and recurrent NPCs, outperforming ¹⁸F-FDG in detecting skull-base invasion and metastases.