Initial Results of<sup>68</sup>Ga-FAPI-46 PET/MRI to Assess Response to Neoadjuvant Chemotherapy in Breast Cancer
Philipp Backhaus, Matthias C. Burg, Inga Asmus, Michaela Pixberg, Florian Büther, Hans‐Jörg Breyholz, Randy Yeh, Stefanie Weigel, Patricia Stichling, Walter Heindel, Stefanie Bobe, P. G. Barth, Joke Tio, Michael Schäfers
Abstract
Improving imaging-based response after neoadjuvant chemotherapy (NAC) in breast cancer assessment could obviate histologic confirmation of pathologic complete response (pCR) and facilitate deescalation of chemotherapy or surgery. Fibroblast activation protein inhibitor (FAPI) PET/MRI is a promising novel molecular imaging agent for the tumor microenvironment with intense uptake in breast cancer. We assessed the diagnostic performance of follow-up breast <sup>68</sup>Ga-FAPI-46 (<sup>68</sup>Ga-FAPI) PET/MRI in classifying the response status of local breast cancer and lymph node metastases after completion of NAC and validated this approach immunohistochemically. <b>Methods:</b> In women who completed NAC for invasive breast cancer, follow-up <sup>68</sup>Ga-FAPI PET/MRI and corresponding fibroblast activation protein (FAP) immunostainings were retrospectively analyzed. Metrics of <sup>68</sup>Ga-FAPI uptake and FAP immunoreactivity in women with or without pCR were compared using the Mann–Whitney <i>U</i> test. Diagnostic performance to detect remnant invasive cancer was calculated for tracer uptake metrics using receiver-operating-characteristic curves and for masked readers’ visual assessment categories of PET/MRI and MRI alone. <b>Results:</b> Thirteen women (mean age ± SD, 47 ± 9 y) were evaluated. Seven of the 13 achieved pCR in the breast and 6 in the axilla. FAP immunoreactivity was significantly associated with response status. The <sup>68</sup>Ga-FAPI PET/MRI mean breast tumor-to-background ratio was 0.9 (range, 0.6–1.2) for pCR and 2.1 (range, 1.4–3.1) for no pCR (<i>P</i> = 0.001). Integrated PET/MRI could classify breast response correctly in all 13 women based on readers’ visual assessment or tumor-to-background ratio. Evaluation of MRI alone resulted in at least 2 false-positives. For lymph nodes, PET/MRI readers had at least 2 false-negative classifications, whereas MRI alone resulted in 2 false-negatives and 1 false-positive. <b>Conclusion:</b> To our knowledge, this was the first analysis of <sup>68</sup>Ga-FAPI PET/MRI for response assessment after NAC for breast cancer. The diagnostic performance of PET/MRI in a small study sample trended toward a gain over MRI alone, clearly supporting future prospective studies.