Validation of parametric analysis of dynamic [¹⁸F]FLT PET in EGFR-mutated NSCLC patients prior and during therapy.

Objectives To validate multiple parametric methods for quantification of [¹⁸F]-Fluorothymidine PET ([¹⁸F]FLT PET) in patients with advanced EGFR mutation positive non-small cell lung carcinoma (NSCLC) treated with gefitinib, an EGFR tyrosine kinase inhibitor (TKI).

Methods Ten NSCLC patients underwent dynamic [¹⁵O]H2O and [¹⁸F]FLT PET/CT at baseline, 7 and 28 days after start of treatment. Venous and arterial samples were collected during PET for metabolite correction of the image-derived input function. Parametric images were generated using plasma input Logan (LGA) and Patlak graphic analysis and two 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 (NLR) of the tumor time activity curve using a 2-tissue compartment reversible model with blood volume fraction¹.

Results After optimizing the settings of each parametric method, distribution volumes (V_T) (Median: 3.46 And IQR: 2.0) obtained with LGA, BFM and SA all correlated well with those derived using NLR at baseline as well as during therapy (R²≥0.98, ICC>0.97 and Slope: 0.853, 1.00 and 1.09 resp. LGA, BFM and SA). BFM and SA also generated accurate K₁ values compared with those from NLR analysis (R²: 0.989, ICC: 0.962, slope: 1.00 and R²: 0.980, ICC: 0.906, slope: 1.00 resp.). Patlak analysis did not provide quantitatively robust K_i values. Perfusion ( [¹⁵O]H2O) was not correlated to V_T and K₁ derived from the various parametric methods.

Conclusions BFM can generate quantitative accurate parametric FLT V_T images in NSCLC patients before and during therapy, while LGA and SA based V_T showed some negative and positive bias respectively. Moreover, BFM provided quantitative accurate parametric K₁ data. We therefore recommend BFM as the preferred parametric method for analysis of dynamic [¹⁸F]FLT PET/CT studies.