[68Ga]Ga-FAPI-04 PET/CT outperforms [18F]FDG-PET/CT in Disease Mapping and Progression Assessment in Metastatic High-Grade Pleomorphic Sarcoma: A Potential for FAPI Theranostics

Pleomorphic sarcoma is an aggressive soft-tissue malignancy with heterogeneous metabolic characteristics and tumor biology. We herein report a 52-year-old woman with metastatic high-grade pleomorphic sarcoma who underwent dual-tracer imaging with [18F]Fluorodeoxyglucose and [68Ga]Ga-Fibroblast activation protein inhibitor (FAPI-04) Positron emission tomography/computed tomography (PET/CT) during disease surveillance. Despite histologically high-grade disease, metastatic lesions demonstrated only low-grade FDG uptake, whereas [68 Ga]Ga-FAPI-04 PET/CT showed intense tracer accumulation with markedly superior lesion conspicuity. On subsequent restaging, [68 Ga]Ga-FAPI-04 PET/CT more accurately delineated progression of pleural disease and identified additional metastatic sites involving the brain, tongue, and contralateral thigh. This case illustrates the unusual ambiguity between histological grade and glucose metabolism, with a high-grade pleomorphic sarcoma showing low FDG avidity. The case highlights the biological heterogeneity of sarcoma, the limitations of FDG PET/CT in selected patients, and the complementary diagnostic and theranostic potential of FAPI PET/CT in high-grade pleomorphic sarcoma. The high FAPI uptake observed across all lesions suggested the potential feasibility of fibroblast activation protein (FAP)-targeted radioligand therapy, expanding the role of FAPI in the theranostic management of sarcoma.