Assessment of Simplified Methods to Measure F-18-FLT Uptake Changes in EGFR-Mutated Non-Small Cell Lung Cancer Patients Undergoing EGFR Tyrosine Kinase Inhibitor Treatment

作者：Frings Virginie; Yaqub Maqsood; Hoyng Lieke L; Golla Sandeep S V; Windhorst Albert D; Schuit Robert C; Lammertsma Adriaan A; Hoekstra Otto S; Smit Egbert F; Boellaard Ronald^*

来源：Journal of Nuclear Medicine, 2014, 55(9): 1417-1423.

DOI：10.2967/jnumed.114.140913

• F-18-FLT
• PET
• NSCLC
• pharmacokinetic modeling
• imaging biomarker

3'-deoxy-3'-F-18-fluorothymidine (F-18-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 F-18-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 receptor mutation were included in this prospective observational study. Patients underwent O-15-H2O and F-18-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 F-18-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 F-18-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) = 0.83-0.97, P < 0.001, slope = 0.72-1.12). F-18-FLT uptake significantly decreased at 7 and 28 d after the start of treatment compared with baseline (P < 0.01). Changes in F-18-FLT uptake were not correlated with changes in perfusion, as measured using O-15-H2O. Conclusion: SUV and TBR could both be used as surrogate simplified measures to assess changes in F-18-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.

• 出版日期2014-9