Per-patient Comparison of [68Ga]-FAPI-46 Versus [18F]FDG as PET Tracers in ER-positive Breast Cancer: Study Design of a Single-centre Prospective Study.

Introduction. [18F]FDG can be considered as PET tracer to determine whole-body staging in patients with locally advanced (LABC), metastatic, and recurrent breast cancer. Yet, previous studies demonstrated a lower amount of metabolic accumulation on [18F]FDG PET in case of oestrogen receptor (ER)-positive breast cancer. Consequently, given the lower metabolic accumulation, patients with ER-positive breast cancer might be at risk for underdiagnosis according to [18F]FDG PET. A novel PET tracer, [68Ga]-fibroblast activation protein inhibitor (FAPI)-46, has shown promising results in breast cancer (re)staging. This single-centre prospective pilot study aims to explore the relative diagnostic accuracy of [68Ga]-FAPI-46 compared to [18F]FDG in patients with ER-positive breast cancer and will provide the required information to support sample size calculation for a future validation study. Methods. In this study, 20 patients with ER-positive LABC, metastatic, or recurrent breast cancer will undergo the standard [18F]FDG PET exam and a [68Ga]-FAPI-46 PET/CT and [68Ga]-FAPI-46 PET/MRI exam. Histopathological confirmation will be obtained in cases of discordant or concordant (double-positive) findings, depending on clinical relevance and technical feasibility. The study will provide preliminary estimates of the relative accuracy of [68Ga]-FAPI-46 PET when compared to [18F]FDG PET as well as the proportion of discordant findings and patients in whom a biopsy is feasible. Conclusions. The present single-centre prospective pilot study will characterize the potential of [68Ga]-FAPI-46 PET to identify additional lesions not detected on a [18F]FDG PET exam in patients with ER-positive breast cancer to estimate an adequate sample size for a future validation study. Trial registration. This study was registered prospectively on ClinicalTrials.gov. Trial registration number: NCT06335069; Register date: 28 March 2024.