Parametric Method Performance for Dynamic 3'-Deoxy-3'-¹⁸F-Fluorothymidine PET/CT in Epidermal Growth Factor...

The objective of this study was to validate several parametric methods for quantification of 3'-deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT) PET in advanced-stage non-small cell lung carcinoma (NSCLC) patients with an activating epidermal growth factor receptor mutation who were treated with gefitinib or erlotinib. Furthermore, we evaluated the impact of noise on accuracy and precision of the parametric analyses of dynamic ¹⁸F-FLT PET/CT to assess the robustness of these methods. Methods Ten NSCLC patients underwent dynamic ¹⁸F-FLT PET/CT at baseline and 7 and 28 d after the start of treatment. Parametric images were generated using plasma input Logan graphic analysis and 2 basis functions-based methods: a 2-tissue-compartment basis function model (BFM) and spectral analysis (SA). Whole-tumor-averaged parametric pharmacokinetic parameters were compared with those obtained by nonlinear regression of the tumor time-activity curve using a reversible 2-tissue-compartment model with blood volume fraction. In addition, 2 statistically equivalent datasets were generated by countwise splitting the original list-mode data, each containing 50% of the total counts. Both new datasets were reconstructed, and parametric pharmacokinetic parameters were compared between the 2 replicates and the original data. Results: After the settings of each parametric method were optimized, distribution volumes (V_T) obtained with Logan graphic analysis, BFM, and SA all correlated well with those derived using nonlinear regression at baseline and during therapy (R² ≥ 0.94; intraclass correlation coefficient > 0.97). SA-based V_T images were most robust to increased noise on a voxel-level (repeatability coefficient, 16% vs. >26%). Yet BFM generated the most accurate K₁ values (R² = 0.94; intraclass correlation coefficient, 0.96). Parametric K₁ data showed a larger variability in general; however, no differences were found in robustness between methods (repeatability coefficient, 80%-84%). Conclusion: Both BFM and SA can generate quantitatively accurate parametric ¹⁸F-FLT V_T images in NSCLC patients before and during therapy. SA was more robust to noise, yet BFM provided more accurate parametric K₁ data. We therefore recommend BFM as the preferred parametric method for analysis of dynamic ¹⁸F-FLT PET/CT studies; however, SA can also be used.