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Parametric imaging of 18F-fluoro-3-deoxy-3-l-fluorothymidine PET data to investigate tumour heterogeneity

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

[18F]Fluoro-3′-deoxy-3′-l-fluorothymidine ([18F]FLT) is a tissue proliferation marker which has been widely validated as a tumour-specific imaging tracer for PET. [18F]FLT uptake in breast cancer is generally quantified at the region level or through first-order statistical descriptors (mean or maximum value), approaches that ignore the known complexity and heterogeneity of cancer tissues. Our aims were: (1) to validate a robust and reproducible voxel-wise approach to the quantification of [18F]FLT PET data in breast cancer patients, and (2) to exploit the entire distribution of the [18F]FLT retention estimates and their variability in the tumour region for the prediction of early treatment response.

Methods

The dataset was derived from 15 patients with stage II–IV breast cancer, scanned twice before chemotherapy and once 1 week after therapy. Using RECIST criteria (after 60 days) nine patients were categorized as responders or nonresponders to treatment. Kinetic modelling (compartmental modelling, Patlak analysis and spectral analysis with iterative filter), tissue-to-plasma ratio and standardized uptake value were applied at the voxel level. Test–retest estimates were used to assess reproducibility and reliability of the [18F]FLT uptake values before and after therapy for responder/nonresponder prediction.

Results

All the methods provided a measure of [18F]FLT uptake that was reliable and reproducible with ICC >0.94. Moreover, a very strong correlation was found among the methods (R 2 > 0.81). All the methods provided a limited number of outliers (<20 % in tumour), with the exception of compartmental modelling (>25 %) which was therefore excluded from the prediction analysis. Differences between before and after therapy in mean voxel-wise uptake in tumour did not allow a complete responder/nonresponder classification. In contrast, considering the full estimate distributions within the tumour (changes in median and mode between before and after therapy) improved therapy response for all the analysed methods.

Conclusion

We showed that kinetic modelling (Patlak and spectral analysis with iterative filter) applied voxel-wise allows appropriate [18F]FLT uptake estimation in breast cancer with good reproducibility. Notably, this study indicated that a more comprehensive statistical investigation could improve tumour characterization and prediction of treatment response.

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Acknowledgement

The authors would like to thank Dr. Julien Williem for his help and support in organizing the dataset.

This research was supported in part by UK Medical Research Council (core grant MC_A652_5PY80, and programme grant “Quantitative methodologies for Positron Emission Tomography”, no. G1100809/1). Portions of this work were presented in preliminary form at International Society of Nuclear Medicine and Molecular Imaging meeting (Vancouver, 2013).

Conflicts on interest

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Authors and Affiliations

  1. Department of Information Engineering (DEI), University of Padova, Via G. Gradenigo 6/B, 35131, Padova, Italy

    M. Veronese, G. Rizzo & A. Bertoldo

  2. Department of Neuroimaging, Institute of Psychiatry, King’s College London, London, UK

    M. Veronese

  3. Comprehensive Cancer Imaging Centre, Imperial College London, London, UK

    E. O. Aboagye

Authors
  1. M. Veronese
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  2. G. Rizzo
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  3. E. O. Aboagye
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  4. A. Bertoldo
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Corresponding author

Correspondence to A. Bertoldo.

Additional information

M. Veronese and G. Rizzo contributed equally to this work.

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Veronese, M., Rizzo, G., Aboagye, E.O. et al. Parametric imaging of 18F-fluoro-3-deoxy-3-l-fluorothymidine PET data to investigate tumour heterogeneity. Eur J Nucl Med Mol Imaging 41, 1781–1792 (2014). https://doi.org/10.1007/s00259-014-2757-z

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  • DOI: https://doi.org/10.1007/s00259-014-2757-z

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