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The uptake of 3′-deoxy-3′-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels

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

Abstract

Purpose

The aim of this study was to investigate the role of thymidine kinase 1 (TK1) protein in 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) studies.

Methods

We investigated the in vivo kinetics of [18F]FLT in TK1+/− and TK1−/− L5178Y mouse lymphoma tumours that express different levels of TK1 protein.

Results

[18F]FLT-derived radioactivity, measured by a dedicated small animal PET scanner, increased within the tumours over 60 min. The area under the normalised tumour time–activity curve were significantly higher for the TK1+/− compared with the −/− variant (0.89±0.02 vs 0.79±0.03 MBq ml−1 min, P=0.043; n=5 for each tumour type). Ex vivo gamma counting of tissues excised at 60 min p.i. (n=8) also revealed significantly higher tumour [18F]FLT uptake for the TK1+/− variant (6.2±0.6 vs 4.6±0.4%ID g−1, P=0.018). The observed differences between the cell lines with respect to [18F]FLT uptake were in keeping with a 48% higher TK1 protein in the TK1+/− tumours versus the −/− variant (P=0.043). On average, there were no differences in ATP levels between the two tumour variants (P=1.00). A positive correlation between [18F]FLT accumulation and TK1 protein levels (r=0.68, P=0.046) was seen. Normalisation of the data for ATP content further improved the correlation (r=0.86, P=0.003).

Conclusion

This study shows that in vivo [18F]FLT kinetics depend on TK1 protein expression. ATP may be important in realising this effect. Thus, [18F]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring.

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Acknowledgements

The study was supported by Cancer Research UK grants C2536/A3554 and C153/A1802. H.B. was supported by a grant awarded by the Leopoldina Society (Halle, Germany) and administered through the German Education and Research Ministry (BMBF-LPD 9901/8-22). The authors also wish to thank Marcel C. Cleij for synthesising the [18F]FLT, Kawai Yau for her assistance in the biodistribution studies and Lynn Maslen for her editorial support in the completion of the manuscript. We are grateful to David Gibbs and Ann Jackman for providing the L5178Y cell lines. The animal experiments were performed by licensed investigators in accordance with the national guidelines [35].

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Authors and Affiliations

  1. Molecular Therapy and PET Oncology Research Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK

    Henryk Barthel, Meg Perumal, John Latigo & Eric O. Aboagye

  2. Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 20A, 04103, Leipzig, Germany

    Henryk Barthel

  3. Clinical Research Laboratory, Department of Oncology, Huddinge University Hospital, Karolinska Institute, 171 76, Stockholm, Sweden

    Qimin He

  4. Hammersmith Imanet, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK

    Frank Brady & Sajinder K. Luthra

  5. Wolfson Molecular Imaging Centre, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK

    Pat M. Price

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Correspondence to Eric O. Aboagye.

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Barthel, H., Perumal, M., Latigo, J. et al. The uptake of 3′-deoxy-3′-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels. Eur J Nucl Med Mol Imaging 32, 257–263 (2005). https://doi.org/10.1007/s00259-004-1611-0

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  • DOI: https://doi.org/10.1007/s00259-004-1611-0

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