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

Validation of [F]FLT as a perfusion-independent imaging biomarker of tumour response in EGFR-mutated NSCLC patients undergoing treatment with an EGFR tyrosine kinase inhibitor.
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Iqbal R, Kramer GM, Frings V, Smit EF, Hoekstra OS, Boellaard R, ,


Iqbal R, Kramer GM, Frings V, Smit EF, Hoekstra OS, Boellaard R, , (click to view)

Iqbal R, Kramer GM, Frings V, Smit EF, Hoekstra OS, Boellaard R, ,

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EJNMMI research 2018 03 278(1) 22 doi 10.1186/s13550-018-0376-6

Abstract
BACKGROUND
3′-Deoxy-3′-[F]fluorothymidine ([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 [F]FLT as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural relationship between [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 [O]HO and [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 [O]HO and proliferation measured with [F]FLT volume of distribution (V). A multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high [F]FLT Vusing a single global threshold for all scans and subjects. By combining these initial classifications, voxels were allocated to four categories (low perfusion-low V, low perfusion-high V, high perfusion-low Vand high perfusion-high V).

RESULTS
A total of 17 perfusion and 18 [F]FLT PET/CT scans were evaluated. The average tumour values across all lesions were 0.53 ± 0.26 mL cm minand 4.25 ± 1.71 mL cmfor perfusion and [F]FLT V, respectively. Multiparametric analysis suggested a shift in voxel distribution, particularly regarding the V: from an average of ≥ 77% voxels classified in the "high Vcategory" to ≥ 85% voxels classified in the "low Vcategory". 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 [F]FLT might be a perfusion-independent PET tracer for measuring tumour response as parametric changes in [F]FLT uptake occurred independent from changes in perfusion.

TRIAL REGISTRATION
Nederlands Trial Register (NTR), NTR3557 . Registered 2 August 2012.

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