Comparison between 68GaGa-FAPI-46 and 18FFDG PET/CT uptake in luminal-like vs. HER2-positive breast cancer

Abstract Background Fibroblast activation protein (FAP)–targeted tracers have emerged as promising agents for breast cancer imaging, with recent studies demonstrating PET performance comparable to or surpassing, that of 18 FFDG. Nevertheless, data comparing 68 GaGa-FAPI-46 and 18 FFDG uptake in hormone receptor and/or HER2–positive breast cancer (luminal-like vs HER2-positive) remain scarce. Aim of this study was to investigate the diagnostic performance of 68 GaGa-FAPI-46 versus 18 FFDG PET/CT in patients with hormone-receptor and/or HER2-positive breast cancer, and to evaluate the uptake of both tracers stratified by molecular subtypes (luminal-like vs HER2-positive). A sub-analysis of a prospective observational trial (NCT04571086) was conducted. Patients with histologically confirmed, hormone receptor- and/or HER2-positive breast cancer who underwent whole-body 68 GaGa-FAPI-46 and 18 FFDG PET/CT in the same week for initial staging or follow-up were included. 68 GaGa-FAPI-46 or 18 FFDG PET-positive lesions were defined as visually increased lesion uptake compared to adjacent organ background. Semi-automatic segmentation was performed to determine SUVmax, SUVpeak, TLRpeak, total number of lesions, total tumour volume, and total tumour SUV mean. Data were compared between molecular subtypes (luminal-like vs HER2-positive). Results Thirteen patients were included. Overall, the detection performance was comparable between 68 GaGa-FAPI-46 and 18 FFDG PET. The semi-quantitative analysis showed comparable mean uptake values in breast cancer lesions on 68 GaGa-FAPI-46 and 18 FFDG PET/CT (SUV max : 13.4 vs. 12.9; TLR peak : 5.6 vs. 4.5) and revealed no significant differences in the median lesion count (4.5 vs. 5), mean total tumour volume (71.5 vs. 73.2 mL), or mean total tumour SUV mean (5.4 vs. 5.4). No substantial differences between molecular subtypes (luminal-like vs. HER2-positive) were observed. Conclusion In this small exploratory cohort, comparable uptake patterns in 68 GaGa-FAPI-46- and 18 FFDG-positive breast cancer lesions were observed across subtypes, underscoring the potential of 68 GaGa-FAPI-46 as a versatile imaging tool. Future studies in larger cohorts are warranted to explore the potential of FAP-targeted theranostics in different breast cancer subtypes. Trial registration 68-Ga-FAPI-PET for Tumor Detection: A Prospective Observational Trial, NCT04571086, 09-15-2020, https://clinicaltrials.gov/study/NCT04571086 .