Triple-tracer PET (18F-FDG, 68Ga-DOTANOC, 68Ga-FAPI) maps inter- and intra-lesional heterogeneity in metastatic high-grade neuroendocrine neoplasms

9.1 ± 3.0), with 23% detected by [68Ga] Ga-FAPI. Lymph nodes exhibited mixed avidity ([18F] FDG 10.2 ± 4.3; [68Ga] Ga- FAPI 7.0 ± 2.7; [68Ga] Ga-DOTANOC 5.2 ± 3.0). Marked inter- and intra-patient heterogeneity was observed across tracers. The combined protocol improved lesion characterization, reduced false negatives, and revealed heterogeneity that would have been underestimated by single-tracer imaging. These findings demonstrate the feasibility and potential clinical utility of integrating [18F] FDG, [68Ga] Ga-DOTANOC and [68Ga] Ga-FAPI PET in high-grade NENs, providing a more comprehensive theranostics roadmap. Given the limited sample size and statistical power, larger prospective studies are warranted to validate these preliminary observations and refine patient selection for multitracer imaging or future "cocktail" therapy strategies.