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Quantification of [18F]afatinib using PET/CT in NSCLC patients: a feasibility study
E A van de Stadt1,2, M Yaqub3,4, A A Lammertsma3,4
1Department of Pulmonology, Amsterdam UMC location VUmc, Amsterdam, the Netherlands. e.vandestadt@amsterdamumc.nl.
Introduction:
Only a subgroup of non-small cell lung cancer (NSCLC) patients benefit from treatment using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as afatinib. Tumour uptake of [18F]afatinib using positron emission tomography (PET) may identify those patients that respond to afatinib therapy. Therefore, the aim of this study was to find the optimal tracer kinetic model for quantification of [18F]afatinib uptake in NSCLC tumours.
Methods:
[18F]Afatinib PET scans were performed in 10 NSCLC patients. The first patient was scanned for the purpose of dosimetry. Subsequent patients underwent a 20-min dynamic [15O]H2O PET scan (370 MBq) followed by a dynamic [18F]afatinib PET scan (342 ± 24 MBq) of 60 or 90 min. Using the Akaike information criterion (AIC), three pharmacokinetic plasma input models were evaluated with both metabolite-corrected sampler-based input and image-derived (IDIF) input functions in combination with discrete blood samples. Correlation analysis of arterial on-line sampling versus IDIF was performed. In addition, perfusion dependency and simplified measures were assessed.
Results:
Ten patients were included. The injected activity of [18F]afatinib was 341 ± 37 MBq. Fifteen tumours could be identified in the field of view of the scanner. Based on AIC, tumour kinetics were best described using an irreversible two-tissue compartment model and a metabolite-corrected sampler-based input function (Akaike 50%). Correlation of plasma-based input functions with metabolite-corrected IDIF was very strong (r2 = 0.93). The preferred simplified uptake parameter was the tumour-to-blood ratio over the 60- to 90-min time interval (TBR60-90). Tumour uptake of [18F]afatinib was independent of perfusion.
Conclusion:
The preferred pharmacokinetic model for quantifying [18F]afatinib uptake in NSCLC tumours was the 2T3K_vb model. TBR60-90 showed excellent correlation with this model and is the best candidate simplified method.
Trial Registration:
https://eudract.ema.europa.eu/ nr 2012-002849-38.
Insights
Positron emission tomography (PET) with [18F]afatinib can identify non-small cell lung cancer (NSCLC) patients who will benefit from EGFR tyrosine kinase inhibitor (TKI) therapy. The irreversible two-tissue compartment model best quantifies tracer uptake.
Area of Science:
- Nuclear medicine imaging
- Pharmacokinetics
- Oncology
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) like afatinib benefit only a subset of non-small cell lung cancer (NSCLC) patients.
- Positron emission tomography (PET) with [18F]afatinib shows potential for identifying responsive NSCLC patients.
- Accurate quantification of [18F]afatinib tumor uptake is crucial for treatment selection.
Purpose of the Study:
- To determine the optimal pharmacokinetic model for quantifying [18F]afatinib uptake in NSCLC tumors.
- To evaluate different input functions and simplified measures for accurate tracer quantification.
- To assess the correlation between various kinetic models and simplified uptake parameters.
Main Methods:
- Dynamic [18F]afatinib PET scans were performed in 10 NSCLC patients.
- Three pharmacokinetic plasma input models were evaluated using metabolite-corrected sampler-based and image-derived input functions.
- The Akaike information criterion (AIC) was used to select the best model.
- Correlation analysis was performed between arterial input functions and image-derived input functions (IDIF).
- Perfusion dependency and simplified uptake measures, such as tumor-to-blood ratio (TBR), were assessed.
Main Results:
- The irreversible two-tissue compartment model (2T3K_vb) with a metabolite-corrected sampler-based input function was the best fit based on AIC.
- A very strong correlation (r2 = 0.93) was observed between plasma-based input functions and metabolite-corrected IDIF.
- The tumor-to-blood ratio over the 60- to 90-min interval (TBR60-90) demonstrated excellent correlation with the preferred pharmacokinetic model.
- Tumor uptake of [18F]afatinib was found to be independent of tumor perfusion.
Conclusions:
- The 2T3K_vb model is the preferred pharmacokinetic model for quantifying [18F]afatinib uptake in NSCLC tumors.
- [18F]afatinib PET imaging can accurately quantify tracer uptake in NSCLC.
- TBR60-90 is a reliable simplified method for assessing [18F]afatinib tumor uptake, correlating well with the gold standard model.
