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

V. Frings, M. Yaqub, L. L. Hoyng, S. S. V. Golla, A. D. Windhorst, R. C. Schuit, A. A. Lammertsma, O. S. Hoekstra, E. F. Smit, R. Boellaard
2014 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
more » ... 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.
doi:10.2967/jnumed.114.140913 pmid:24970910 fatcat:m57hw77ixzaalda5z4qsjbgdci