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

J Nucl Med. 2014 Sep;55(9):1417-23. doi: 10.2967/jnumed.114.140913. Epub 2014 Jun 26.

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.

Conclusion: 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.

Keywords: 18F-FLT; NSCLC; PET; imaging biomarker; pharmacokinetic modeling.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Dideoxynucleosides*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • 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*

Substances

  • Dideoxynucleosides
  • Fluorine Radioisotopes
  • Protein Kinase Inhibitors
  • Radiopharmaceuticals
  • EGFR protein, human
  • ErbB Receptors
  • alovudine