FAPI Radionuclide Theranostics Show Promise in Sarcoma Diagnosis and Treatment
A systematic review indicates FAPI PET outperforms standard imaging for detecting sarcoma lesions while FAPI radionuclide therapy demonstrates clinical activity.
Key takeaways
- FAPI PET demonstrated a pooled detection rate of 89.7% for all sarcoma lesions and 91.3% for distant metastases, outperforming standard FDG PET.
- In high-grade sarcomas, mean or median FAPI PET maximum standardized uptake values (SUVmax) ranged from 9.5 to 30.2, compared to 6.4 to 21.1 in low-grade tumors.
- Radionuclide therapy targeting FAP achieved a 64.7% disease control rate in 34 treated patients, with grade 3 or higher adverse events in only two individuals.
Sarcomas represent a heterogeneous group of malignant neoplasms arising from mesenchymal tissue. Because these tumors are challenging to diagnose and treat, researchers have focused on the tumor microenvironment for novel molecular targets. Fibroblast activation protein (FAP), which is highly expressed in this environment, has emerged as an attractive target for molecular imaging.
A systematic review published in the journal Annals of Nuclear Medicine in September 2026 evaluated the utility of fibroblast activation protein inhibitor (FAPI)-based radionuclide theranostics in sarcoma. The analysis searched PubMed, Embase, and Web of Science for studies published between 2018 and 2025 to synthesize evidence on both the diagnostic accuracy of FAPI imaging and the safety and efficacy of FAPI-targeted therapy.
Sarcomas present significant clinical hurdles in both accurate staging and effective treatment. By targeting FAP, which is highly expressed in the tumor microenvironment, FAPI-based imaging and therapy offer a dual-purpose theranostic approach. This review provides pooled data comparing FAPI directly to standard imaging, while also assessing the safety of FAPI-targeted therapy.
What Happened
Following PRISMA guidelines, the authors of the review evaluated 12 studies comprising 398 total patients.
For diagnosis, six studies involving 361 patients and 2,477 lesions were analyzed. The quality of these diagnostic studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. FAPI PET achieved a pooled detection rate of 89.7% for all sarcoma lesions and 91.3% for distant metastases. This was higher than standard [18 F]FDG PET, which demonstrated detection rates of 72.1% for all lesions and 74.0% for distant metastases.
The review also analyzed tracer uptake values. In high-grade sarcomas, the mean or median maximum standardized uptake value (SUVmax) for FAPI PET ranged from 9.5 to 30.2. In low-grade tumors, the mean or median SUVmax ranged from 6.4 to 21.1.
For treatment, five studies involving 34 patients evaluated FAPI radionuclide therapy (RLT). Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), the therapy showed a disease control rate of 64.7%. Favorable safety was observed, with grade 3 or higher adverse events occurring in only two patients.
What The Evidence Shows
The systematic review analyzed 12 studies published between 2018 and 2025, representing 398 patients. Diagnostic findings in 361 patients (2,477 lesions) demonstrated that FAPI PET had a pooled detection rate of 89.7% for all lesions and 91.3% for distant metastases, compared to 72.1% and 74.0% for [18 F]FDG PET. Therapeutic findings in 34 patients demonstrated a 64.7% disease control rate using RECIST 1.1, with only two patients experiencing grade 3 or higher adverse events.
What We Don't Know Yet
The provided source text does not detail specific patient characteristics, the exact sarcoma subtypes included in the heterogeneous group, or the specific radionuclides utilized in the therapeutic studies. Additionally, the patient sample size for the therapeutic analysis was small, involving only 34 patients. The source notes that further studies are needed to confirm the usefulness of FAPI in grading, staging, and treating sarcoma.
What Comes Next
The systematic review states that further studies are needed to confirm the usefulness of FAPI-based tools in the grading, staging, and treatment of sarcoma. The source does not specify concrete ongoing trials or planned timelines for these future investigations.
What This Means
The findings suggest that FAPI PET provides a clear advantage over conventional [18 F]FDG PET for systemic lesion detection, which may improve the staging accuracy of sarcomas. For treatment, FAPI radionuclide therapy represents a potentially safe and active therapeutic modality, characterized by high disease control and minimal severe adverse events.
Original Source
PubMed (NCBI E-utilities): https://pubmed.ncbi.nlm.nih.gov/42704611/
Questions readers ask
- How does FAPI PET compare to standard FDG PET for sarcoma imaging?
- According to the systematic review, FAPI PET achieved a pooled detection rate of 89.7% for all sarcoma lesions and 91.3% for distant metastases. Standard [18 F]FDG PET showed lower detection rates of 72.1% and 74.0%, respectively.
- What is the disease control rate for FAPI radionuclide therapy in sarcoma?
- In the five therapeutic studies analyzed, which included a total of 34 patients, FAPI radionuclide therapy achieved a disease control rate of 64.7% based on RECIST 1.1 criteria.
- Are there significant side effects associated with FAPI radionuclide therapy?
- The systematic review reported that FAPI radionuclide therapy demonstrated a favorable safety profile, with adverse events of grade 3 or higher occurring in only two patients out of the 34 evaluated.
What this means
The findings suggest that FAPI PET provides a clear advantage over conventional [18 F]FDG PET for systemic lesion detection, which may improve the staging accuracy of sarcomas. For treatment, FAPI radionuclide therapy represents a potentially safe and active therapeutic modality, characterized by high disease control and minimal severe adverse events.
Limitations and uncertainties
- The provided source text does not detail specific patient characteristics, the exact sarcoma subtypes included in the heterogeneous group, or the specific radionuclides utilized in the therapeutic studies. Additionally, the patient sample size for the therapeutic analysis was small, involving only 34 patients. The source notes that further studies are needed to confirm the usefulness of FAPI in grading, staging, and treating sarcoma.
