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

R. Iqbal, G. M. Kramer, V. Frings, E. F. Smit, O. S. Hoekstra, R. Boellaard, on behalf of the QuIC-ConCePT Consortium

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: 3′-Deoxy-3′-[18F]fluorothymidine ([18F]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 [18F]FLT as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural relationship between [18F]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 [15O]H2O and [18F]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 [15O]H2O and proliferation measured with [18F]FLT volume of distribution (VT). A multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high [18F]FLT VT using a single global threshold for all scans and subjects. By combining these initial classifications, voxels were allocated to four categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results: A total of 17 perfusion and 18 [18F]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 [18F]FLT VT, respectively. Multiparametric analysis suggested a shift in voxel distribution, particularly regarding the VT: from an average of ≥ 77% voxels classified in the “high VT category” to ≥ 85% voxels classified in the “low VT 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 [18F]FLT might be a perfusion-independent PET tracer for measuring tumour response as parametric changes in [18F]FLT uptake occurred independent from changes in perfusion. Trial registration: Nederlands Trial Register (NTR), NTR3557. Registered 2 August 2012.

Original languageEnglish
Article number22
JournalEJNMMI Research
Volume8
DOIs
Publication statusPublished - 1 Jan 2018

Cite this

@article{f5e41778417a4e1eb5300f6740d96904,
title = "Validation of [18F]FLT as a perfusion-independent imaging biomarker of tumour response in EGFR-mutated NSCLC patients undergoing treatment with an EGFR tyrosine kinase inhibitor",
abstract = "Background: 3′-Deoxy-3′-[18F]fluorothymidine ([18F]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 [18F]FLT as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural relationship between [18F]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 [15O]H2O and [18F]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 [15O]H2O and proliferation measured with [18F]FLT volume of distribution (VT). A multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high [18F]FLT VT using a single global threshold for all scans and subjects. By combining these initial classifications, voxels were allocated to four categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results: A total of 17 perfusion and 18 [18F]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 [18F]FLT VT, respectively. Multiparametric analysis suggested a shift in voxel distribution, particularly regarding the VT: from an average of ≥ 77{\%} voxels classified in the “high VT category” to ≥ 85{\%} voxels classified in the “low VT 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 [18F]FLT might be a perfusion-independent PET tracer for measuring tumour response as parametric changes in [18F]FLT uptake occurred independent from changes in perfusion. Trial registration: Nederlands Trial Register (NTR), NTR3557. Registered 2 August 2012.",
keywords = "Non-small cell lung cancer (NSCLC), Perfusion, Positron emission tomography (PET), Tyrosine kinase inhibitors (TKIs), [F]FLT",
author = "R. Iqbal and Kramer, {G. M.} and V. Frings and Smit, {E. F.} and Hoekstra, {O. S.} and R. Boellaard and {on behalf of the QuIC-ConCePT Consortium}",
year = "2018",
month = "1",
day = "1",
doi = "10.1186/s13550-018-0376-6",
language = "English",
volume = "8",
journal = "EJNMMI Research",
issn = "2191-219X",
publisher = "Springer Berlin",

}

Validation of [18F]FLT as a perfusion-independent imaging biomarker of tumour response in EGFR-mutated NSCLC patients undergoing treatment with an EGFR tyrosine kinase inhibitor. / Iqbal, R.; Kramer, G. M.; Frings, V.; Smit, E. F.; Hoekstra, O. S.; Boellaard, R.; on behalf of the QuIC-ConCePT Consortium.

In: EJNMMI Research, Vol. 8, 22, 01.01.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Validation of [18F]FLT as a perfusion-independent imaging biomarker of tumour response in EGFR-mutated NSCLC patients undergoing treatment with an EGFR tyrosine kinase inhibitor

AU - Iqbal, R.

AU - Kramer, G. M.

AU - Frings, V.

AU - Smit, E. F.

AU - Hoekstra, O. S.

AU - Boellaard, R.

AU - on behalf of the QuIC-ConCePT Consortium

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: 3′-Deoxy-3′-[18F]fluorothymidine ([18F]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 [18F]FLT as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural relationship between [18F]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 [15O]H2O and [18F]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 [15O]H2O and proliferation measured with [18F]FLT volume of distribution (VT). A multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high [18F]FLT VT using a single global threshold for all scans and subjects. By combining these initial classifications, voxels were allocated to four categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results: A total of 17 perfusion and 18 [18F]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 [18F]FLT VT, respectively. Multiparametric analysis suggested a shift in voxel distribution, particularly regarding the VT: from an average of ≥ 77% voxels classified in the “high VT category” to ≥ 85% voxels classified in the “low VT 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 [18F]FLT might be a perfusion-independent PET tracer for measuring tumour response as parametric changes in [18F]FLT uptake occurred independent from changes in perfusion. Trial registration: Nederlands Trial Register (NTR), NTR3557. Registered 2 August 2012.

AB - Background: 3′-Deoxy-3′-[18F]fluorothymidine ([18F]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 [18F]FLT as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural relationship between [18F]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 [15O]H2O and [18F]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 [15O]H2O and proliferation measured with [18F]FLT volume of distribution (VT). A multiparametric classification was performed by classifying voxels as low and high perfusion and/or low and high [18F]FLT VT using a single global threshold for all scans and subjects. By combining these initial classifications, voxels were allocated to four categories (low perfusion-low VT, low perfusion-high VT, high perfusion-low VT and high perfusion-high VT). Results: A total of 17 perfusion and 18 [18F]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 [18F]FLT VT, respectively. Multiparametric analysis suggested a shift in voxel distribution, particularly regarding the VT: from an average of ≥ 77% voxels classified in the “high VT category” to ≥ 85% voxels classified in the “low VT 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 [18F]FLT might be a perfusion-independent PET tracer for measuring tumour response as parametric changes in [18F]FLT uptake occurred independent from changes in perfusion. Trial registration: Nederlands Trial Register (NTR), NTR3557. Registered 2 August 2012.

KW - Non-small cell lung cancer (NSCLC)

KW - Perfusion

KW - Positron emission tomography (PET)

KW - Tyrosine kinase inhibitors (TKIs)

KW - [F]FLT

UR - http://www.scopus.com/inward/record.url?scp=85044723263&partnerID=8YFLogxK

U2 - 10.1186/s13550-018-0376-6

DO - 10.1186/s13550-018-0376-6

M3 - Article

VL - 8

JO - EJNMMI Research

JF - EJNMMI Research

SN - 2191-219X

M1 - 22

ER -