Radiolabeled fibroblast activation protein inhibitor PET/computed tomography imaging in invasive lobular breast cancer: a narrative review and research agenda

Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as an investigational alternative which targets cancer-associated fibroblasts, abundant in the ILC tumor stroma. This narrative review synthesizes emerging evidence on radiolabeled FAPI PET/CT in ILC and highlights potential advantages, limitations, and research gaps. A purposive literature search of SCOPUS, PubMed/MEDLINE, and Web of Science up to August 2025 identified 10 clinical publications, including three prospective studies, two retrospective comparisons, and five case reports; mixed-cohort studies were included when ILC-specific findings were extractable. Across these small, heterogeneous early studies, gallium-68 FAPI PET/CT consistently demonstrated higher tumor uptake and greater lesion conspicuity than 18F-FDG PET/CT in several ILC-relevant scenarios, particularly infiltrative soft-tissue metastases, peritoneal and serosal involvement, and sclerotic osseous lesions. Comparative studies also reported identification of additional multifocal or multicentric primary foci and greater nodal involvement, while case reports described enhanced visualization of gastric, orbital, peritoneal, and ovarian metastases, sites often inconspicuous on 18F-FDG PET/CT. Despite these promising findings, available evidence remains limited, predominantly observational, and lacks lesion-level histopathologic confirmation, standardized imaging protocols, and data on management impact or patient outcomes. Overall, early results suggest that gallium-68 FAPI PET/CT may offer improved lesion conspicuity in selected ILC settings; however, these observations remain hypothesis generating. Larger, multicentre prospective studies with standardized acquisition parameters, rigorous lesion validation, and clinically meaningful endpoints are required to establish the diagnostic and therapeutic relevance of FAPI PET/CT and determine whether it has a role in the routine clinical evaluation of ILC.