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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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    Authors
    Barthel, Henryk
    Perumal, Meg
    Latigo, John
    He, Qimin
    Brady, Frank
    Luthra, Sajinder K
    Price, Patricia M
    Aboagye, E O
    Affiliation
    Molecular Therapy and PET Oncology Research Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
    Issue Date
    2005-03
    
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    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.
    Citation
    The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels. 2005, 32 (3):257-63 Eur. J. Nucl. Med. Mol. Imaging
    Journal
    European Journal of Nuclear Medicine and Molecular Imaging
    URI
    http://hdl.handle.net/10541/75883
    DOI
    10.1007/s00259-004-1611-0
    PubMed ID
    15791434
    Type
    Article
    Language
    en
    ISSN
    1619-7070
    ae974a485f413a2113503eed53cd6c53
    10.1007/s00259-004-1611-0
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