Validation of [(18)F]FLT as a perfusion-independent imaging biomarker of tumour response in EGFR-mutated NSCLC patients undergoing treatment with an EGFR tyrosine kinase inhibitor

BACKGROUND: 3′-Deoxy-3′-[(18)F]fluorothymidine ([(18)F]FLT) was proposed as an imaging biomarker for the assessment of in vivo cellular proliferation with positron emission tomography (PET). The current study aimed to validate [(18)F]FLT as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural relationship between [(18)F]FLT uptake and perfusion in non-small cell lung cancer (NSCLC) patients undergoing treatment with a tyrosine kinase inhibitor (TKI). Six patients with metastatic NSCLC, having an activating epidermal growth factor receptor (EGFR) mutation, were included in this study. Patients underwent [(15)O]H(2)O and [(18)F]FLT PET/CT scans at three time points: before treatment and 7 and 28 days after treatment with a TKI (erlotinib or gefitinib). Parametric analyses were performed to generate quantitative 3D images of both perfusion measured with [(15)O]H(2)O and proliferation measured with [(18)F]FLT volume of distribution (V(T)). A multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high [(18)F]FLT V(T) using a single global threshold for all scans and subjects. By combining these initial classifications, voxels were allocated to four categories (low perfusion-low V(T), low perfusion-high V(T), high perfusion-low V(T) and high perfusion-high V(T)). RESULTS: A total of 17 perfusion and 18 [(18)F]FLT PET/CT scans were evaluated. The average tumour values across all lesions were 0.53 ± 0.26 mL cm(− 3) min(− 1) and 4.25 ± 1.71 mL cm(− 3) for perfusion and [(18)F]FLT V(T), respectively. Multiparametric analysis suggested a shift in voxel distribution, particularly regarding the V(T): from an average of ≥ 77% voxels classified in the “high V(T) category” to ≥ 85% voxels classified in the “low V(T) category”. The shift was most prominent 7 days after treatment and remained relatively similar afterwards. Changes in perfusion and its spatial distribution were minimal. CONCLUSION: The present study suggests that [(18)F]FLT might be a perfusion-independent PET tracer for measuring tumour response as parametric changes in [(18)F]FLT uptake occurred independent from changes in perfusion. TRIAL REGISTRATION: Nederlands Trial Register (NTR), NTR3557. Registered 2 August 2012 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13550-018-0376-6) contains supplementary material, which is available to authorized users.