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Fibroblast Activation Protein Inhibitor Theranostics in Sarcoma

Esmail JafariDepartment of Nuclear Medicine, The Persian Gulf Nuclear Medicine Research Center, Molecular Imaging, and Theranostics, Bushehr Medical University Hospital, School of Medicine, Bushehr University of Medical Sciences, Bushehr, IranMalik JuweidDepartment of Radiology and Nuclear Medicine, Division of Nuclear MedicineNarges JokarDepartment of Nuclear Medicine, The Persian Gulf Nuclear Medicine Research Center, Molecular Imaging, and Theranostics, Bushehr Medical University Hospital, School of Medicine, Bushehr University of Medical Sciences, Bushehr, IranNader ShakibazadDepartment of Pediatrics, Division of Hematology/Oncology, Bushehr Medical University Hospital, School of Medicine, Bushehr University of Medical SciencesSeyed Javad RekabpourDepartment of Oncology, Salman Farsi Hospital, Bushehr, IranMajid AssadiDepartment of Nuclear Medicine, The Persian Gulf Nuclear Medicine Research Center, Molecular Imaging, and Theranostics, Bushehr Medical University Hospital, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
Clinical Nuclear Medicinejournal2026en
ABI

Annotatsiya

Sarcomas are rare and heterogeneous cancers arising from mesenchymal tissues, presenting diagnostic and therapeutic challenges. Fibroblast activation protein (FAP), overexpressed in the tumor microenvironment of many sarcomas, has emerged as a promising theranostic target. FAP inhibitors (FAPI)-PET/CT demonstrates excellent sensitivity and specificity in detecting primary tumors, local recurrence, and distant metastases, even in low-grade sarcomas. This facilitates accurate staging and personalized treatment. Various FAPI radiotracers, including FAPI-04, FAPI-46, and FAP-2286, offer unique pharmacokinetic properties. FAPI-targeted radionuclide therapy (TRT) employs therapeutic radioisotopes to deliver targeted radiation to FAP-expressing tumor cells. Early clinical trials show promising disease control rates and manageable toxicity profiles. However, challenges remain, including FAP expression heterogeneity and the need for optimized treatment protocols. The aim of this review is to provide a comprehensive overview of the current evidence and future directions of FAPI-based theranostics in sarcoma management, highlighting its potential to improve patient outcomes.

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