Comparison of [18F]PFPN and [18F]FDG PET in Mucosal Melanoma: Diagnostic Performance, Staging Impact, and Correlation with Molecular Markers

PURPOSE: The study aims to compare the diagnostic performance of the novel melanin-targeted [18F]-N-(2-(diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)picolinamide ([18F]PFPN) positron emission tomography (PET) and [18F]fluorodeoxyglucose ([18F]FDG) PET in mucosal melanoma, evaluate their impact on clinical staging, and assess correlations between imaging metrics and molecular markers. EXPERIMENTAL DESIGN: This prospective study enrolled 65 participants with histologically confirmed mucosal melanoma from February 2021 to January 2025. All participants underwent both [18F]FDG PET and [18F]PFPN PET within 1 week. Lesion- and participant-based analyses compared detection sensitivity, false-positive rate, and staging concordance. Quantitative PET parameters were analyzed, and correlations with HMB45, SOX10, MelanA, S100, and mutation status (BRAF, KIT, NRAS) were evaluated using nonparametric tests and correlation analysis with Bonferroni correction. Decision curve analysis was used to evaluate clinical benefit. RESULTS: Sixty-five participants were included. [18F]PFPN PET showed higher lesion-based sensitivity than [18F]FDG PET [363/399 (91%) vs. 332/399 (83.2%)] and no false positives [0/363 (0%) vs. 4/336 (1.2%)]. The normalized maximum standardized uptake value was significantly higher for [18F]PFPN across all lesion types (P < 0.05). PFPN-based staging was more consistent with clinical staging (6.2% vs. 18.5% discordant cases). [18F]PFPN uptake showed significant positive correlations with HMB45 and SOX10 expression, whereas [18F]FDG parameters showed no such associations. CONCLUSIONS: [18F]PFPN PET outperforms [18F]FDG PET in lesion detection and clinical staging in mucosal melanoma, especially for liver and bone metastases. Its association with melanin differentiation markers may support its use in personalized imaging strategies.