(68)Ga-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

(68)Ga-labeled fibroblast activation protein inhibitor ((68)Ga-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 (18)F-FDG PET/CT. Here, we aimed to evaluate the suitability of (68)Ga-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 (68)Ga-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 (R(2) = 0.822; P = 0.001) and metastatic lymph nodes (R(2) = 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 (68)Ga-FAPI PET/CT were positively correlated with fibroblast activation protein expression (P < 0.001 for both). Conclusion: Assessment of early changes in (68)Ga-FAPI uptake during NAC by (68)Ga-FAPI PET/CT can predict pCR and primary tumor concentric withdrawal in BC patients. (68)Ga-FAPI PET/CT has great potential for the early and late prediction of the pathologic response to NAC in BC.