Head-to-head comparison of FDG vs FAPI 04 PET CT for breast cancer

Introduction: Breast cancer is the most common malignancy in women. However, the role of FDG PET-CT is rather limited in well differentiated, hormone expressing, lobular variant and luminal A tumours. Fibroblast activation protein (FAP) is expressed in cancer associated fibroblasts of breast cancer. FAPI 04 is a small molecule inhibitor of FAP. Ga-68 FAPI 04 (FAPI) PET CT imaging has shown promising results compared to FDG in various malignancies. The aim was to compare the roles of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in the staging of primary breast cancer as well as in metastasis evaluation of recurrent breast cancer.

Methods: This is a retrospective study comparing FDG and FAPI PET CT scans in breast cancer patients. Study period was between January 2021 to August 2022, in a quaternary care institution. A total of 34 female patients underwent both FAPI and FDG PET CT within a span of 2 days. Demographic details, histopathologic findings including IHC markers, grading and variant of breast cancer, visual and semiquantitative analysis of both PET CT scans were analysed. Histopathology for staging and follow-up scans for recurrence were used as reference standards respectively. Mood’s median test and Mann-Whitney U test were implemented for non-parametric pairwise comparison between variables.

Results: A total of 84 scans (42 each for FDG and FAPI) for 34 patients including follow-up scans were performed. The indication was staging in 33/42 (79%) and recurrence evaluation in 9/42 (21%) patients. Luminal A subgroup seen in13/42 (31%), Luminal B in 20/42(48%), triple negative group in 8/42 (19%) and Her2 type in one patient (2%). Mean primary tumour size is 24mm(±23mm). Mean SUVmax of primary in FDG is 6.55 (±7.0) and FAPI is 9.26 (±7.2) with p-value of 0.02. TBR (Tumour background ratio) for primary lesion in FDG is 5.06 and for FAPI is 7.91 with a p-value of 0.03. However no significant difference is seen in the nodal/background ratio between FDG and FAPI. 15/42 (35%) had distant metastasis with significant difference in the number of skeletal, hepatic and other metastatic sites (p<0.05).

Conclusions: Higher tumour background ratio and increased metastatic site detection is seen in FAPI compared to FDG PET CT in staging and recurrence of breast cancer. FAPI opens a new paradigm in breast cancer imaging with potential impact in diagnosis and management. Further FAPI has a promising theranostic value for breast cancer in future.

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