FAP-targeted PET/CT imaging in patients with breast cancer from a prospective bi-center study: insights into...

To evaluate the diagnostic accuracy and clinical impact of fibroblast activation protein (FAP)-targeted PET/CT imaging in primary and metastatic breast cancer and compare the results with those of standard-of-care imaging (SCI) and [¹⁸F]FDG PET/CT.

We prospectively analyzed patients with diagnosed or suspected breast cancer who underwent concomitant FAP-targeted PET/CT (radiotracers including either [⁶⁸Ga]Ga-FAPI-46 or [¹⁸F]FAPI-42) and [¹⁸F]FDG PET/CT scans from June 2020 to January 2024 at two medical centers. Breast ultrasound (US) imaging was performed in all treatment-naïve patients as SCI. The SUVmax, tumor-to-background ratio (TBR), lesion detection rate, and tumor-node-metastasis (TNM) classifications between FAP-targeted and [¹⁸F]FDG PET/CT were evaluated and compared.

Sixty-one female patients (median age, 52 y; range, 28-82 y) were included. Among them, 23 patients underwent evaluation for a definitive diagnosis of suspected breast lesions, 15 underwent initial staging, and 23 were evaluated for the detection of recurrence. The sensitivities of breast US, [¹⁸F]FDG, and FAP-targeted PET/CT for detecting primary breast tumors were 82%, 79%, and 100%, respectively. Regarding the diagnosis of recurrent/metastatic lesions, the lesion-based detection rate of FAP-targeted PET/CT was significantly higher than that of [¹⁸F]FDG, which included local and regional recurrence, neck lymph node (LN), abdomen LN, bone, and liver metastases. Compared with [¹⁸F]FDG PET/CT, FAP-targeted PET/CT altered thirteen patients' TNM staging/restaging (13/59, 22%) and nine patients' clinical management (9/59, 15%). Compared to SCI, FAPI changed fourteen patients' TNM staging/re-staging (14/59, 24%) and eleven patients' therapeutic regimens(11/59, 19%). There was no significant association between FAPI-derived SUVmax and receptor status/histologic type in both primary and metastatic lesions.

FAP-targeted PET/CT was superior to [¹⁸F]FDG in diagnosing primary and metastatic breast cancer, with higher radiotracer uptake and TBR, especially in the detection of primary/recurrent tumors, abdominal LN metastases, liver, and bone metastases. FAP-targeted PET/CT is superior to [¹⁸F]FDG and SCI in TNM staging and may improve tumor staging, recurrence detection, and implementation of necessary treatment modifications.