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

• Published in: The Journal of nuclear medicine (1978) Vol. 55; no. 9; pp. 1417 - 1423
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States 01-09-2014
• Subjects: Aged; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Dideoxynucleosides; Female; Fluorine Radioisotopes; Humans; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; Mutation; Prospective Studies; Protein Kinase Inhibitors - therapeutic use; Radionuclide Imaging; Radiopharmaceuticals; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; 18F-FLT; imaging biomarker; NSCLC; PET; pharmacokinetic modeling
• ISSN: 1535-5667
• DOI: 10.2967/jnumed.114.140913

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).
Ten patients with metastatic NSCLC harboring an activating epidermal growth factor receptor mutation were included in this prospective observational study. Patients underwent (15)O-H2O 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.
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) = 0.83-0.97, P < 0.001, slope = 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-H2O.
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.