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

Heinzmann, K; Honess, DJ; Lewis, DY; Smith, D-M; Cawthorne, C; Keen, H; Heskamp, S; ... Brindle, KM; + view all (2016) The relationship between endogenous thymidine concentrations and [F-18]FLT uptake in a range of preclinical tumour models. EJNMMI RESEARCH , 6 , Article 63. 10.1186/s13550-016-0218-3. Green open access

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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.

Type: Article
Title: The relationship between endogenous thymidine concentrations and [F-18]FLT uptake in a range of preclinical tumour models
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13550-016-0218-3
Publisher version: http://dx.doi.org/10.1186/s13550-016-0218-3
Language: English
Additional information: © 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.
Keywords: Science & Technology, Life Sciences & Biomedicine, Radiology, Nuclear Medicine & Medical Imaging, [F-18]Fluorothymidine, Plasma, Tumour, Thymidine, Preclinical Pet, Positron-Emission-Tomography, In-Vivo, Proliferation, Cancer, PET
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1508626
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