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

Egbert F. Smit¹  for the QuIC-ConCePT Consortium¹  Maqsood Yaqub¹  Virginie Frings¹  Robert C. Schuit¹  Albert D. Windhorst¹  Sandeep S.V. Golla¹  Otto S. Hoekstra¹  Ronald Boellaard¹  Adriaan A. Lammertsma¹  Lieke L. Hoyng¹ 

关键词: ¹⁸F-FLT;    PET;    NSCLC;    pharmacokinetic modeling;    imaging biomarker;   

DOI  :  10.2967/jnumed.114.140913

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

3′-deoxy-3′-18F-fluorothymidine (18F-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 18F-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 15O-H2O and 18F-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 18F-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 18F-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 (r2 = 0.83–0.97, P < 0.001, slope = 0.72–1.12). 18F-FLT uptake significantly decreased at 7 and 28 d after the start of treatment compared with baseline (P < 0.01). Changes in 18F-FLT uptake were not correlated with changes in perfusion, as measured using 15O-H2O. Conclusion: SUV and TBR could both be used as surrogate simplified measures to assess changes in 18F-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.

【 授权许可】

Unknown