68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT for the Early and Late Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Prospective Study

Abstract

⁶⁸Ga-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) PET/CT has demonstrated promising clinical results, with a higher SUV_max and tumor-to-background ratio (TBR) in breast cancer (BC) patients than ¹⁸F-FDG PET/CT. Here, we aimed to evaluate the suitability of ⁶⁸Ga-FAPI PET/CT for the early and late prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in BC.

Methods:
Twenty-two consecutive patients with newly diagnosed BC and an indication for NAC were prospectively included. All patients underwent standard chemotherapy and ⁶⁸Ga-FAPI PET/CT at baseline, after 2 cycles of NAC (PET2), and 1 wk before surgery (PET3). SUV_max was measured in the primary tumor region and positive regional lymph nodes. The expression of fibroblast activation protein in the primary lesion was analyzed by immunohistochemistry.

Results:
Seven patients (31.8%) achieved a pathologic complete response (pCR), and 15 (68.2%) had residual tumors. Thirteen patients (59.1%) showed concentric withdrawal of the primary tumor, and 9 (40.9%) showed diffuse withdrawal. Between PET2 and PET3, the ΔSUV_max of the primary tumor (R² = 0.822; P = 0.001) and metastatic lymph nodes (R² = 0.645; P = 0.002) were significantly correlated. The absolute values of SUV_max and TBR at PET2 and PET3 were lower in patients with pCR than in those without pCR (P < 0.05). Moreover, a larger ΔSUV_max at any time point was strongly associated with pCR (P < 0.05). Similar downward trends in SUV_max, TBR, and ΔSUV_max were observed in the pattern of primary tumor reduction. For predicting pCR, the optimal cutoff values for ΔSUV_max after 2 chemotherapy cycles, ΔSUV_max before surgery, TBR after 2 chemotherapy cycles, and TBR before surgery of the primary tumor were 3.4 (area under the curve [AUC], 0.890), 1.1 (AUC, 0.978), −63.8% (AUC, 0.879), −90.8% (AUC, 0.978), 7.6 (AUC, 0.848), and 1.4 (AUC, 0.971), respectively. Immunohistochemistry showed that the SUV_max and TBR of ⁶⁸Ga-FAPI PET/CT were positively correlated with fibroblast activation protein expression (P < 0.001 for both).

Conclusion:
Assessment of early changes in ⁶⁸Ga-FAPI uptake during NAC by ⁶⁸Ga-FAPI PET/CT can predict pCR and primary tumor concentric withdrawal in BC patients. ⁶⁸Ga-FAPI PET/CT has great potential for the early and late prediction of the pathologic response to NAC in BC.