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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.03.2005 | Original Article

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

verfasst von: Henryk Barthel, Meg Perumal, John Latigo, Qimin He, Frank Brady, Sajinder K. Luthra, Pat M. Price, Eric O. Aboagye

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 3/2005

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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.

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Titel: The uptake of 3′-deoxy-3′-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels
verfasst von: Henryk Barthel
Meg Perumal
John Latigo
Qimin He
Frank Brady
Sajinder K. Luthra
Pat M. Price
Eric O. Aboagye
Publikationsdatum: 01.03.2005
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 3/2005
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-004-1611-0

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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