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Updated: Sep 26, 2025
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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Interobserver Agreement Rates on Fibroblast Activation Protein Inhibitor-Directed Molecular Imaging and Therapy
Sebastian E Serfling1, Philipp E Hartrampf1, Yingjun Zhi2
1From the Department of Nuclear Medicine, University Hospital Würzburg.
Objectives:
Fibroblast activation protein (FAP) has emerged as a novel target for FAP inhibitor (FAPI)-directed molecular imaging and endoradiotherapy (ERT). We aimed to assess the interobserver agreement rates for interpretation of 68Ga-FAPI-4 PET/CT and decision for ERT.
Patients And Methods:
A random order of 68Ga-FAPI-4 PET/CTs from 49 oncology patients were independently interpreted by 4 blinded readers. Per scan, visual assessment was performed, including overall scan impression, number of organ/lymph node (LN) metastases, and number of affected organs/LN regions. Moreover, a maximum of 3 target lesions, defined as largest in size and/or most intense, per organ compartment were identified, which allowed for an additional quantitative interobserver assessment of LN and organ lesions. To investigate potential reference tissues, quantification also included unaffected liver parenchyma and blood pool. Readers also had to indicate whether FAPI-directed ERT should be considered (based on intensity of uptake and widespread disease). Interobserver agreement rates were evaluated using intraclass correlation coefficients (ICCs) and interpreted according to Cicchetti (with 0.4-0.59 indicating fair, and 0.6-0.74 good, agreement).
Results:
On a visual basis, the agreement rate for an overall scan impression was fair (ICC, 0.42; 95% confidence interval [CI], 0.27-0.57). The concordance rate for number of affected LN areas was also fair (ICC, 0.59; 95% CI, 0.45-0.72), whereas the number of LN metastases, number of affected organs, and number of organ metastases achieved good agreement rates (ICC, ≥0.63). In a quantitative analysis, concordance rates for LN were good (ICC, 0.70; 0.48-0.88), but only fair for organ lesions (ICC, 0.43; 0.26-0.60). In regards to background tissues, ICCs were good for unaffected liver parenchyma (0.68; 0.54-0.79) and fair for blood pool (0.43; 0.29-0.58). When readers should decide on ERT, concordance rates were also fair (ICC, 0.59; 95% CI, 0.46-0.73).
Conclusions:
For FAPI-directed molecular imaging and therapy, a fair to good interobserver agreement rate was achieved, supporting the adoption of this radiotracer for clinical routine and multicenter trials.
Insights
Interobserver agreement for 68Ga-FAPI-4 PET/CT interpretation and therapy decisions showed fair to good rates. This supports the clinical use of fibroblast activation protein inhibitor (FAPI)-directed imaging and endoradiotherapy (ERT).
Area of Science:
- Oncology
- Nuclear Medicine
- Radiochemistry
Background:
- Fibroblast activation protein (FAP) is a key target for novel cancer therapies.
- FAP inhibitor (FAPI)-directed molecular imaging and endoradiotherapy (ERT) offer promising treatment avenues.
- Accurate interpretation of 68Ga-FAPI-4 PET/CT is crucial for patient selection and treatment planning.
Purpose of the Study:
- To evaluate the interobserver agreement in interpreting 68Ga-FAPI-4 PET/CT scans.
- To assess agreement on decisions for FAPI-directed endoradiotherapy (ERT).
- To determine the reliability of 68Ga-FAPI-4 PET/CT for clinical routine and multicenter trials.
Main Methods:
- 49 oncology patients' 68Ga-FAPI-4 PET/CT scans were independently reviewed by 4 blinded readers.
- Visual and quantitative assessments of scan findings, including metastases and affected regions, were performed.
- Interobserver agreement was quantified using intraclass correlation coefficients (ICCs).
Main Results:
- Fair agreement (ICC, 0.42) was observed for overall scan impression.
- Good agreement rates (ICC, ≥0.63) were achieved for the number of lymph node metastases and organ metastases.
- Fair agreement (ICC, 0.59) was noted for ERT decision-making.
Conclusions:
- Fair to good interobserver agreement was achieved for 68Ga-FAPI-4 PET/CT interpretation and ERT decisions.
- These findings support the integration of FAPI-directed molecular imaging and therapy into clinical practice.
- The study validates the potential of 68Ga-FAPI-4 PET/CT for routine use and multicenter investigations.
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