Title |
The relationship between endogenous thymidine concentrations and [18F]FLT uptake in a range of preclinical tumour models
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Published in |
EJNMMI Research, August 2016
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DOI | 10.1186/s13550-016-0218-3 |
Pubmed ID | |
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 |
Recent studies have shown that 3'-deoxy-3'-[(18)F] fluorothymidine ([(18)F]FLT)) uptake depends on endogenous tumour thymidine concentration. The purpose of this study was to investigate tumour thymidine concentrations and whether they correlated with [(18)F]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 [(18)F]FLT uptake, described by the maximum and mean tumour-to-liver uptake ratio (TTL) and SUV. 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 [(18)F]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. Endogenous tumour thymidine concentrations alone are not predictive of [(18)F]FLT uptake in murine cancer models. |
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