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Methodological Considerations in Quantification of 3'-Deoxy-3'-[18F]Fluorothymidine Uptake Measured with Positron Emission Tomography in Patients with Non-Small Cell Lung Cancer

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Abstract

Purpose

To investigate the effect of image-derived input functions (IDIF), input function corrections and volume of interest (VOI) size in quantification of [18F]FLT uptake in non-small cell lung cancer (NSCLC) patients.

Procedures

Twenty-three NSCLC patients were scanned on a HR+ scanner. IDIFs were defined over the aorta and left ventricle. Activity concentration and metabolite fraction were measured in venous blood samples. Venous blood samples at 30, 40 and 60 min after injection were used to calibrate the IDIF time–activity curves. Adaptive thresholds were used for VOI definition. Full kinetic analysis and simplified measures were performed.

Results

Non-linear regression analysis showed better fits for the irreversible model compared to the reversible model in the majority. Calibrated and metabolite corrected plus plasma-to-blood ratio corrected input function resulted in high correlations between SUV and Patlak K i (Pearson correlation coefficients 0.86–0.96, p value < 0.001). No significant differences in correlation between SUV and Patlak K i were observed with variation of IDIF structure or VOI size.

Conclusions

Plasma-to-blood ratio correction, metabolite correction and calibration improved the correlation between SUV and Patlak K i significantly, indicating the need for these corrections when K i is used to validate semi-quantitative measures, such as SUV.

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Acknowledgements

We thank the patients and their families for participating in this study. In addition, we acknowledge the staff of the Department of Nuclear Medicine and PET Research of the VU University Medical Center, Amsterdam, The Netherlands, for their help with tracer production and data collection.

Conflict of Interest Statement

QuIC-ConCePT is supported by the IMI-JU European funding and by the in-kind contribution of the pharmaceutical company members of consortium. The Authors are members of the QuIC-ConCePT project partly funded by EFPIA companies and the Innovative Medicine Initiative Joint Undertaking (IMI-JU) under Grant Agreement No. 115151.

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Correspondence to Ronald Boellaard.

Additional information

The following authors are members of the QuIC-ConCePT Consortium: Virginie Frings, Maqsood Yaqub, Otto S. Hoekstra, Ronald Boellaard.

Appendix

Appendix

QuIC-ConCePT Consortium participants include: AstraZeneca, European Organisation for Research and Treatment of Cancer (EORTC), Cancer Research UK (CRUK), Cambridge Research Institute—CRUK, University of Manchester, Westfälische Wilhelms-Universitat Munster, Radboud University Nijmegen Medical Center, Institut National de la Sante et de la Recherche Medical, Stichting Maastricht Radiation Oncology ‘Maastro Clinic’, VUmc Amsterdam, King’s College London, Universitair Ziekenhuis Antwerpen, Institute of Cancer Research—Royal Cancer Hospital, Erasmus Universitair Medisch Centrum Rotterdam, Imperial College of Science Technology and Medicine, Keosys S.A.S., Eidgenossische Technische Hochschule Zurich, Amgen NV, Eli Lilly and Company Ltd, GlaxoSmithKline Research & Development Limited, Merck KGa, Pfizer Limited, F. Hoffmann—La Roche Ltd., Sanofi-Aventis Research and Development.

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Frings, V., de Langen, A.J., Yaqub, M. et al. Methodological Considerations in Quantification of 3'-Deoxy-3'-[18F]Fluorothymidine Uptake Measured with Positron Emission Tomography in Patients with Non-Small Cell Lung Cancer. Mol Imaging Biol 16, 136–145 (2014). https://doi.org/10.1007/s11307-013-0658-3

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