FAPI Versus 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Breast Cancer

Introduction: Breast cancer (BC) is both the most commonly occurring malignancy and the leading cause of cancer death among women worldwide. 18F-FDG PET/CT has limitations including false positives in inflammatory breast lesions and reduced sensitivity in specific breast cancer subtypes. Previous small-sample retrospective studies suggested that 68Ga-FAPI might outperform 18F-FDG PET/CT with its high sensitivity in the detection of primary tumors and metastases among BC patients. FAPI could be radio-labeled with different radio-nuclides including 68Ga and 18F, and few published studies have focused on the 18F-labeled FAPI among BC patients. This study assesses FAPI (including both 68Ga-FAPI-04 and Al18F-FAPI-04) PET/CT for systemic staging of newly diagnosed BC, compared with 18F-FDG PET/CT.

Methods: Patients with newly diagnosed BC confirmed by biopsy or surgery were enrolled. Patients received FAPI (68Ga-FAPI-04 or Al18F-FAPI-04) and 18F-FDG PET/CT after enrollment. MIM software was used for PET/CT analysis. Two experienced nuclear medicine physicians, who were blinded to the pathological diagnosis and other imaging results, assessed the PET/CT images separately. Any disagreement was resolved by discussion with a third experienced physician. The lesion was recorded as positive if its uptake exceeded that of the adjacent background tissue. The clinical stage was determined from 18F-FDG and FAPI PET/CT, according to the American Joint Committee on Cancer (AJCC) Staging Manual.

Results: A total of 121 patients with BC were included in the analysis. All patients underwent 18F-FDG PET/CT. 53 patients underwent 68Ga-FAPI-04 PET/CT and the other 68 patients underwent Al18F-FAPI-04 PET/CT. Compared to the clinical TNM stage determined by 18F-FDG PET/CT, FAPI PET/CT upstaged 2/29 (6.9%) initial stage IA patients, 10/46 (21.7%) initial stage IIA patients, and 4/34 (11.8%) initial stage IIB patients, whereas down-staged 1/46 (2.2%) initial stage IIA patients, 7/34 (20.6%) initial stage IIB patients. Totally, 19.8% (24/121) of patients were restaged by FAPI PET/CT. The evaluation of axillary lymph node (ALN) status by FAPI PET/CT restaged 14.0% (17/121) of patients, among whom 8 patients were correctly upstaged by the identification of ALN metastases on FAPI PET/CT, and 7 patients were correctly down-staged by the judgment of negative ALN on FAPI PET/CT. The other 7 patients who were upstaged by FAPI PET/CT included one patient having metastases in bone confirmed by biopsy, one patient in ipsilateral supraclavicular LN and five patients in ipsilateral internal mammary LN . Furthermore, the management plans were optimized in 6 patients due to additional detection of bone lesions and internal mammary LNs.

Conclusions: 70.8% of patients who were clinically re-staged by FAPI PET/CT were due to improved ALN status assessment. FAPI PET/CT upstaged 21.7% of stage IIA patients by 18F-FDG PET/CT. Patients with stage IIA BC should be considered for systemic staging with FAPI PET/CT at the time of initial diagnosis.