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

Introduction.[ 18 F]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 [ 18 F]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 [ 18 F]FDG PET.A novel PET tracer, [ 68 Ga]-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 [ 68 Ga]-FAPI-46 compared to [ 18 F]FDG in patients with ERpositive 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 [ 18 F]FDG PET exam and a [ 68 Ga]-FAPI-46 PET/CT and [ 68 Ga]-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 [ 68 Ga]-FAPI-46 PET when compared to [ 18 F]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 [ 68 Ga]-FAPI-46 PET to identify additional lesions not detected on a [ 18 F]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.