The Role of [68Ga]Ga FAPi PET/CT in Staging and Restaging in Breast Cancer with Low FDG Uptake

Background Breast cancer is a highly heterogeneous disease, with different histopathologic subtypes exhibiting distinct biological behaviour and metabolic characteristics. While [¹⁸F]-FDG PET/CT is widely used for staging and restaging, its effectiveness is limited in tumors with low glucose metabolism, such as lobular carcinoma. In recent years, fibroblast activation protein inhibitor (FAPi)-based imaging with [⁶⁸Ga]Ga-FAPI PET/CT has emerged as a promising alternative, offering improved lesion detection in tumors with low FDG avidity. This study aims to evaluate the potential efficacy of [⁶⁸Ga]Ga-FAPi PET/CT in staging and restaging breast cancer patients with FDG-negative or low FDG uptake lesions. Results Twenty nine female patients referred for staging, restaging or investigation of recurrence were performed [ ¹⁸ F]-FDG PET/CT and [ ⁶⁸ Ga]Ga-FAPi PET/CT. The mean age was 57.7 ± 11.6 years. Histopathologic examination from previous surgeries/biopsies available for 24 patients revealed lobular carcinoma in 16 cases, ductal carcinoma in 6 cases, signet ring cell carcinoma in one patient and mucinous cell carcinoma in one patient. In seven patients (24.1%), neither the [ ¹⁸ F]-FDG PET/CT nor the [ ⁶⁸ Ga]Ga-FAPi PET/CT revealed any findings indicating recurrence or metastasis. Disease stage increased in 44.8% (n = 13) of patients after [ ⁶⁸ Ga]Ga-FAPi PET/CT imaging, with 10 of them showing no pathologic findings on [ ¹⁸ F]-FDG PET/CT; after [ ⁶⁸ Ga]Ga-FAPi PET/CT imaging, 9 patients progressed to stage 4 and 1 to stage 3. One patient progressed from stage 1 to stage 2, one progressed from stage 2 to 3 and other patient 3 to stage 4 according to AJCC 8th edition. Fifty percent (n = 8) of the lobular carcinomas were upstaged after [ ⁶⁸ Ga]Ga-FAPi PET/CT. The detection of lymph nodes and distant metastases in lobular carcinoma was higher with [ ⁶⁸ Ga]Ga-FAPi PET/CT than with [ ¹⁸ F]-FDG PET/CT. Furthermore, [ ⁶⁸ Ga]Ga-FAPi PET/CT showed a higher SUVmax in primary tumor foci and metastases (p < 0.05). Conclusion [ ⁶⁸ Ga]Ga FAPi PET/CT has been shown to be superior for staging and restaging indications in breast cancer, especially for tumors such as lobular carcinoma with low FDG affinity. It is anticipated that [ ⁶⁸ Ga]Ga FAPi PET/CT will play an important role in future guidelines for primary diagnosis and staging in breast cancer patients, especially in patients with the lobular histopathologic subtype.