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The relationship between endogenous thymidine concentrations and [18F]FLT uptake in a range of preclinical tumour models

Heinzmann, Kathrin; Honess, Davina Jean; Lewis, David Yestin; Smith, Donna-Michelle; Cawthorne, Christopher; Keen, Heather; Heskamp, Sandra; Schelhaas, Sonja; Witney, Timothy Howard; Soloviev, Dmitry; Williams, Kaye Janine; Jacobs, Andreas Hans; Aboagye, Eric Ofori; Griffiths, John Richard; Brindle, Kevin Michael

Authors

Kathrin Heinzmann

Davina Jean Honess

David Yestin Lewis

Donna-Michelle Smith

Christopher Cawthorne

Heather Keen

Sandra Heskamp

Sonja Schelhaas

Timothy Howard Witney

Dmitry Soloviev

Kaye Janine Williams

Andreas Hans Jacobs

Eric Ofori Aboagye

John Richard Griffiths

Kevin Michael Brindle



Abstract

Background
Recent studies have shown that 3′-deoxy-3′-[18F] fluorothymidine ([18F]FLT)) uptake depends on endogenous tumour thymidine concentration. The purpose of this study was to investigate tumour thymidine concentrations and whether they correlated with [18F]FLT uptake across a broad spectrum of murine cancer models. A modified liquid chromatography-mass spectrometry (LC-MS/MS) method was used to determine endogenous thymidine concentrations in plasma and tissues of tumour-bearing and non-tumour bearing mice and rats. Thymidine concentrations were determined in 22 tumour models, including xenografts, syngeneic and spontaneous tumours, from six research centres, and a subset was compared for [18F]FLT uptake, described by the maximum and mean tumour-to-liver uptake ratio (TTL) and SUV.

Results
The LC-MS/MS method used to measure thymidine in plasma and tissue was modified to improve sensitivity and reproducibility. Thymidine concentrations determined in the plasma of 7 murine strains and one rat strain were between 0.61 ± 0.12 μM and 2.04 ± 0.64 μM, while the concentrations in 22 tumour models ranged from 0.54 ± 0.17 μM to 20.65 ± 3.65 μM. TTL at 60 min after [18F]FLT injection, determined in 14 of the 22 tumour models, ranged from 1.07 ± 0.16 to 5.22 ± 0.83 for the maximum and 0.67 ± 0.17 to 2.10 ± 0.18 for the mean uptake. TTL did not correlate with tumour thymidine concentrations.

Conclusions
Endogenous tumour thymidine concentrations alone are not predictive of [18F]FLT uptake in murine cancer models.

Journal Article Type Article
Publication Date Dec 1, 2016
Journal EJNMMI Research
Print ISSN 2191-219X
Electronic ISSN 2191-219X
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 6
Issue 1
Article Number 63
APA6 Citation Heinzmann, K., Honess, D. J., Lewis, D. Y., Smith, D., Cawthorne, C., Keen, H., …Brindle, K. M. (2016). The relationship between endogenous thymidine concentrations and [18F]FLT uptake in a range of preclinical tumour models. EJNMMI Research, 6(1), doi:10.1186/s13550-016-0218-3
DOI https://doi.org/10.1186/s13550-016-0218-3
Keywords [18F]Fluorothymidine; Plasma; Tumour; Thymidine; Preclinical PET
Publisher URL https://ejnmmires.springeropen.com/articles/10.1186/s13550-016-0218-3
Related Public URLs https://www.repository.cam.ac.uk/handle/1810/260243
Copyright Statement © The Author(s). 2016

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Copyright Statement
© The Author(s). 2016

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.





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