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

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Heinzmann, Kathrin 
Honess, Davina Jean 
Lewis, David Yestin 
Smith, Donna-Michelle 
Cawthorne, Christopher 


BACKGROUND: 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. 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 [(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. CONCLUSIONS: Endogenous tumour thymidine concentrations alone are not predictive of [(18)F]FLT uptake in murine cancer models.



Plasma, Preclinical PET, Thymidine, Tumour, [18F]Fluorothymidine

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Springer Science and Business Media LLC
Cancer Research UK (CB4110)
Cancer Research Uk (None)
Cancer Research UK (CB4100)
Cancer Research UK (C14303/A17197)
Innovative Medicines Initiative Joint Undertaking (EU FP7/2007-2013) (Grant ID: 115151); Cancer Research UK (Grant ID: 17242, Cancer Research UK-Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester (reference 16465), Grant ID: A11562)