Assessment of Simplified Methods to Measure 18F-FLT Uptake Changes in EGFR-Mutated Non-Small Cell Lung Cancer Patients Undergoing EGFR Tyrosine Kinase Inhibitor Treatment
Journal of Nuclear Medicine
3′-deoxy-3′-18 F-fluorothymidine ( 18 F-FLT) PET/CT provides a noninvasive assessment of proliferation and, as such, could be a valuable imaging biomarker in oncology. The aim of the present study was to assess the validity of simplified quantitative parameters of 18 F-FLT uptake in non-small cell lung cancer (NSCLC) patients before and after the start of treatment with a tyrosine kinase inhibitor (TKI). Methods: Ten patients with metastatic NSCLC harboring an activating epidermal growth factor
... ermal growth factor receptor mutation were included in this prospective observational study. Patients underwent 15 O-H 2 O and 18 F-FLT PET/CT scanning on 3 separate occasions: within 7 d before treatment, and 7 and 28 d after the first therapeutic dose of a TKI (gefitinib or erlotinib). Dynamic scans were acquired and venous blood samples were collected during the 18 F-FLT scan to measure parent fraction and plasma and whole-blood radioactivity concentrations. Simplified measures (standardized uptake value [SUV] and tumor-to-blood ratio [TBR]) were correlated with fully quantitative measures derived from kinetic modeling. Results: Twenty-nine of thirty 18 F-FLT PET/CT scans were evaluable. According to the Akaike criterion, a reversible 2-tissue model with 4 rate constants and blood volume parameter was preferred in 84% of cases. Relative therapy-induced changes in SUV and TBR correlated with those derived from kinetic analyses (r 2 5 0.83-0.97, P , 0.001, slope 5 0.72-1.12). 18 F-FLT uptake significantly decreased at 7 and 28 d after the start of treatment compared with baseline (P , 0.01). Changes in 18 F-FLT uptake were not correlated with changes in perfusion, as measured using 15 O-H 2 O. Conclusion: SUV and TBR could both be used as surrogate simplified measures to assess changes in 18 F-FLT uptake in NSCLC patients treated with a TKI, at the cost of a small underestimation in uptake changes or the need for a blood sample and metabolite measurement, respectively.