title: 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.
abstract: 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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Virginie
authors: V
authors: Frings
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Maqsood
authors: M
authors: Yaqub
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Lieke L
authors: LL
authors: Hoyng
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Sandeep S V
authors: SS
authors: Golla
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Albert D
authors: AD
authors: Windhorst
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Robert C
authors: RC
authors: Schuit
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Adriaan A
authors: AA
authors: Lammertsma
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: Otto S
authors: OS
authors: Hoekstra
authors: Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Egbert F
authors: EF
authors: Smit
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and r.boellaard@vumc.nl.
authors: Ronald
authors: R
authors: Boellaard
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D015224:Dideoxynucleosides; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals
chemical_list: D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D047428:Protein Kinase Inhibitors; D019275:Radiopharmaceuticals; C512478:EGFR protein, human; D066246:ErbB Receptors; C002854:alovudine
keywords: 18F-FLT; NSCLC; PET; imaging biomarker; pharmacokinetic modeling