Physiological uptake characteristics of breast on 68Ga-FAPI-04 PET

Purpose: Gallium 68 ( 68 Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET is sensitive on breast cancer staging, but its clinical utility may be limited by the high physiological FAPI uptake in normal breast tissue that can obscure primary tumors. The aim of this study was to elucidate the characteristics of physiological 68 Ga-FAPI-04 uptake in normal breast. Procedures A total of 143 consecutive women with 68 Ga-FAPI-04 PET were reviewed retrospectively. SUV max , density and thickness of breast gland, as well as SUV max of nipple, were measured. Univariate and multivariate regression analyses were used to identify factors related to the breast and nipple SUVs. Results: Twenty-eight premenopausal, 62 menopausal and 10 post-operative (after bilateral adnexectomy) women with 103 examinations were included. All had a diffuse, symmetrical uptake in breast gland. There was no difference in FAPI uptake between bilateral breasts ( P =  0.253). Patients in menstrual status with expected high estrogen level (late follicular, ovulatory and mid luteal phases) had higher breast SUVs (median, 3.91) than those with expected moderate (early follicular, early luteal and late luteal phases; median, 1.57; P  < 0.001) or low level (menopause and post-operation; median, 0.98; P  < 0.001). Menstrual status was an independent predictors of breast SUV ( r 2  = 0.689, P  < 0.001). All the patients had a focal, symmetrical uptake in nipples. Nipple SUV did not correlate with menstrual status ( P  = 0.913). Conclusion: Physiological breast FAPI uptake levels are related to menstrual status. Premenopausal patients with breast lesions should be examined 68 Ga-FAPI-04 PET during the perimenstrual period (five days before and during menstruation).