Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in patients with breast cancer

Introduction: Small molecule-based fibroblast activation protein inhibitor (FAPi) PET/CT imaging technique has added a new approach to imaging various cancers. This study aimed to compare the diagnostic performance of [⁶⁸Ga]Ga-DOTA.SA.FAPi with that of [¹⁸F]F-FDG PET/CT in detecting primary and metastatic lesions of breast cancer.

Methods: Histologically proven breast cancer patients who underwent [¹⁸F]F-FDG and [⁶⁸Ga]Ga-DOTA.SA.FAPi PET/CT between April 2019 through August 2022 was retrospectively analyzed. Both imaging modalities were compared according to patient-based and lesion-based analysis. The qualitative analysis involved visual judgment of radiotracer uptake which was validated by the morphological findings on diagnostic CT (reference standard). Quantitative comparisons between the radiotracers were presented as standardized uptake value (SUV) corrected for lean body mass: SULpeak, SULavg, and tumor-to-background ratio (TBR).

Results: Forty-seven patients with a mean age of 44.8 ± 9.9 years (range: 31 – 66 years) were evaluated. 85% of patients had invasive ductal carcinoma, and 15% had invasive lobular carcinoma. 12 patients had a triple-negative disease, 17 had HER2-positive, and 18 had HER2-negative disease. 95.5% of patients had distant metastases, and in three patients the disease was locally advanced. 40 patients underwent surgery and the remaining did not. Quantitatively, the tracer uptake [SULpeak, SULavg, and the median tumor-to-background ratio (TBR)] was significantly higher in [⁶⁸Ga]Ga-DOTA.SA.FAPi PET/CT than with [¹⁸F]F-FDG for lymph nodes, pleural metastases, and liver lesions (p<0.05). However, for brain metastasis, only the median TBR was significantly higher (p<0.05) compared to [¹⁸F]F-FDG. In patient-based analysis the sensitivity of [⁶⁸Ga]Ga-DOTA.SA.FAPi PET/CT was higher than that of [¹⁸F]F-FDG PET/CT in the detection of both primary tumors and metastatic lesions. According to lesion-based analysis, on diagnostic CT, 47 patients had 44 primary tumors, 248 lymph nodes, 15 pleural, 88 liver, and 42 brain metastases. [⁶⁸Ga]Ga-DOTA.SA.FAPi scan identified more abnormal lesions than [¹⁸F]F-FDG in all the primary and metastatic sites with a maximum marked difference in the primary site [88.6% vs 81.8% (39 vs. 36 compared to 44 lesions on CT), lymph nodes [89.1% vs 83.8%; P-0.0001(221 vs. 208 compared to 248 lesions on CT)], pleural metastases [93.3% vs 73%; P-0.096 (14 vs. 11 compared to 15 lesions on CT)], and brain metastasis [100% vs 59.5%; P-0.0001 (42 vs. 25 compared to 42 lesions on CT)]

Conclusions: [⁶⁸Ga]Ga-DOTA.SA.FAPi PET/CT was superior to [¹⁸F]F-FDG PET/CT in the imaging of breast cancers.