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Fibroblast Activation Protein Inhibitor Theranostics in Sarcoma: Current Evidence and Future Directions

Esmail Jafari1, Malik E Juweid2,3, Narges Jokar1

  • 1Department 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 Medicine
|February 25, 2026
PubMed

Insights

Fibroblast activation protein (FAP) imaging and therapy show promise for sarcoma management. FAP inhibitors (FAPI) PET/CT accurately detects tumors, while FAPI-targeted radionuclide therapy offers new treatment options.

Area of Science:

  • Oncology
  • Radiochemistry
  • Nuclear Medicine

Background:

  • Sarcomas are rare, heterogeneous cancers with significant diagnostic and therapeutic challenges.
  • Fibroblast activation protein (FAP) is overexpressed in the tumor microenvironment of many sarcomas, making it a potential theranostic target.

Purpose of the Study:

  • To provide a comprehensive overview of fibroblast activation protein inhibitors (FAPI)-based theranostics in sarcoma management.
  • To highlight the potential of FAPI-based approaches to improve patient outcomes in sarcoma.

Main Methods:

  • Review of current evidence on FAPI-PET/CT for sarcoma detection and staging.
  • Analysis of FAPI-targeted radionuclide therapy (TRT) in early clinical trials.
  • Discussion of various FAPI radiotracers (e.g., FAPI-04, FAPI-46, FAP-2286) and their properties.

Main Results:

  • FAPI-PET/CT demonstrates high sensitivity and specificity for detecting primary sarcomas, recurrence, and metastases, including low-grade types.
  • FAPI-TRT shows promising disease control rates and manageable toxicity in early studies.
  • Various FAPI radiotracers offer distinct pharmacokinetic profiles for optimized theranostic applications.

Conclusions:

  • FAPI-based theranostics represent a significant advancement in sarcoma management, enabling accurate staging and personalized treatment.
  • FAPI-TRT holds potential for targeted radiation delivery to FAP-expressing sarcoma cells.
  • Further research is needed to address FAP expression heterogeneity and optimize treatment protocols for improved patient outcomes.
Keywords:
PET/CTfibroblast activation protein inhibitor (FAPI)molecular imagingsarcomatargeted radionuclide therapy (TRT)theranostics

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