The role of 68Ga-FAPi PET/CT in Staging and Restaging of Breast Cancer Subtypes with Limited 18F-FDG Uptake.

OBJECTIVES: Breast cancer is highly heterogeneous, and certain histopathologic subtypes-particularly invasive lobular carcinoma-exhibit low glucose metabolism that limits 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) performance. Fibroblast activation protein inhibitor (FAPi) imaging with Gallium-68 (68Ga)-FAPi PET/CT has emerged as a promising alternative for such tumors. The aim of this study was to evaluate the efficacy of 68Ga-FAPi PET/CT in staging, restaging, and recurrence detection of breast cancer, with emphasis on subtypes for which 18F-FDG PET/CT has low sensitivity. METHODS: Twenty-nine women with pathologically confirmed breast cancer (mean age 57.7±11.6 years) were prospectively enrolled. Histopathology (available in 24 patients) showed lobular carcinoma in 16, ductal carcinoma in 6, signet ring cell carcinoma in 1, and mucinous carcinoma in 1. All underwent both 68Ga-FAPi and 18F-FDG PET/CT within one week for staging or restaging. Maximum standardized uptake values (SUVmax) of primary tumors and metastases were recorded for both tracers and compared using paired t-tests. RESULTS: In 7/29 patients (24.1%), neither 18F-FDG PET/CT nor 68Ga-FAPi PET/CT detected pathological findings. Disease stage increased in 13/29 (44.8%) after 68Ga-FAPi PET/CT, including 10 patients with no pathologic findings on 18F-FDG PET/CT; nine were upstaged to stage 4 and one to stage 3. Additionally, one patient progressed from stage 1 to 2, one from 2 to 3, and another from 3 to 4. Among patients with lobular carcinoma, 8/16 (50%) were upstaged with 68Ga-FAPi PET/CT. Detection of nodal and distant metastases in lobular carcinoma was higher with 68Ga-FAPi than 18F-FDG. 68Ga-FAPi PET/CT also demonstrated higher SUVmax in primary lesions and metastases (p<0.05). CONCLUSION: 68Ga-FAPi PET/CT provides a significant advantage for staging and restaging breast cancer-especially lobular carcinoma and other low 18F-FDG-avid subtypes-supporting its potential role in clinical decision-making and treatment planning.