The relationship between endogenous thymidine concentrations and [18F]FLT uptake in a range of preclinical tumour models
Posted on 2016-08-11 - 05:00
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.
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Heinzmann, Kathrin; Honess, Davina; Lewis, David; Smith, Donna-Michelle; Cawthorne, Christopher; Keen, Heather; et al. (2017). The relationship between endogenous thymidine concentrations and [18F]FLT uptake in a range of preclinical tumour models. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.3697000.v1
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AUTHORS (15)
KH
Kathrin Heinzmann
DH
Davina Honess
DL
David Lewis
DS
Donna-Michelle Smith
CC
Christopher Cawthorne
HK
Heather Keen
SH
Sandra Heskamp
SS
Sonja Schelhaas
TW
Timothy Witney
DS
Dmitry Soloviev
KW
Kaye Williams
AJ
Andreas Jacobs
EA
Eric Aboagye
JG
John Griffiths
KB
Kevin Brindle