Head to head comparison of 68Ga-FAPI-46 PET/CT and 18-FDG PET/CT in breast carcinoma staging: a clinical trial update from Azerbaijan

Introduction: Breast cancer is the most frequently diagnosed cancer and is the leading cause of cancer death in women worldwide. Accurate clinical staging is important for treatment management of breast cancer, but 18FDG PET/CT has some limitations. Labeling fibroblast-activation protein (FAP) with PET radiotracers is a new alternative tool for the visualization of tumor stroma since it is overexpressed in cancer-associated fibroblasts of several tumor entities. The aim of this study is to compare the diagnostic performance of 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT in primary and metastatic lesions of breast cancer and to reveal the best diagnostic imaging time of 68Ga-FAPI-46 PET/CT.

Methods: We have included 75 consecutive naive breast carcinoma patients with median age, 53 years (IQR, 44–62 years). The pathology was confirmed by lesion tru-cut biopsy. 18FDG and [68Ga]FAPI-46 PET/CT exam performed to all patients within 2 days. Statistical analysis techniques were used in order to compare tracer uptakes and to assess the relationship between values.

Patients have been scanned 10 minute, 30 minute and 1 hour after 68Ga-FAPI-46 injection. To find out the highest tumor-to-background ratio, SUVmean values from aorta blood pool and liver parenchyma were chosen as background. To standardize the ratio values, the new variable was defined as the percentage of the 10th, 30th and 60th minute scan time. A one-way repeated measures ANOVA was conducted to determine whether there were statistically significant differences in tumor-to-background over the scan time.

Results: Tracer uptake was higher with [68Ga]FAPI-46 PET/CT than with 18F-FDG PET/CT in primary lesions (SUVmax: 16.6 vs 11.6, respectively, p<0.001) and there were significant moderate correlation with each other (rs=0.311, p=0.007). Significant difference was also found between [68Ga]FAPI-46 and 18F-FDG PET/CT SUVmax values of involved lymph nodes (11.0 vs 8.6, P=0.042, N=50), and there were significant moderate correlation with each other (rs=0.461, p=0.001). There was a significant increase in difference of SUVmax values when the lesion size decreased. In lesions smaller than 1.5 cm, FAPI-46 and 18F-FDG SUVmax values were 12.3 and 5.4, respectively (p=0.004).

There was no statistically significant correlation between tumor SUVmax values and pathology grade (rs(21)=0.089, p=0.70, n=24), along with Ki67 index (rs(16)=0.076, p=0.78, n=24)as well as tumor SUVmax values and patients’ ages (rs(24)=0.036, p=0.87, n=24), along with Ki67 index (rs(16)=0.076, p=0.78, n=24).

68Ga-FAPI-46 PET/CT revealed extra lesions in eleven patients which had not been found with FDG (second lesion in the same breast, n=7; distant lymph node metastases, n=3; and metastases to rib, n=1). Twenty one out of 75 patients had mild to high FAPI-46 uptake in benign inflammatory and degenerative changes.

The tumor-to-background ratio values increased over the 10th, 30th and 60th minute scan time (F(2, 40)=10.95, p=0.002). Post hoc analysis with a Bonferroni adjustment revealed that when aorta SUVmean values taken as a background, 30th minute tumor-to-background ratio was significantly higher than 10th minute scan values (63.3% (95% CI, 24.3 to 102.3), p=0.001), while we did not observe such difference in 60th minute scan (-7.1% (95% CI, -33.6 to 19.3), p=1.000). When liver SUVmean values taken as a background, we observed the similar patterns: 30th minute/10th minute scan (77.1% (95% CI, 47.7 to 107.2), p <0.001), 30th minute/60th minute scan (-8.6% (95% CI, -32.0 to 14.8), p=1.000).

Conclusions: [68Ga]FAPI-46 PET/CT is a new game changer diagnostic method in breast cancer treatment management. In contrast to 18F-FDG, no diet or fasting in preparation is necessary, and scans can be started even 30 minute after injection. Better tumor-to-background ratio and precise lymph node detection of FAPI-46, may indicate potential tool for targeted radionuclide treatment with beta and alpha emitters in the near future.