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

K. Heinzmann; D.J. Honess; D.Y. Lewis; D.-M. Smith; C. Cawthorne; H. Keen; S. Heskamp; S. Schelhaas; Timothy Howard Witney; D. Soloviev; K.J. Williams; A.H. Jacobs; E.O. Aboagye; J.R. Griffiths; K.M. Brindle

doi:10.1186/s13550-016-0218-3

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

K. Heinzmann, D.J. Honess, D.Y. Lewis, D.-M. Smith, C. Cawthorne, H. Keen, S. Heskamp, S. Schelhaas, Timothy Howard Witney, D. Soloviev, K.J. Williams, A.H. Jacobs, E.O. Aboagye, J.R. Griffiths, K.M. Brindle

Imaging Chemistry & Biology

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Journal	EJNMMI Research
Volume	6
Issue number	1
DOIs	https://doi.org/10.1186/s13550-016-0218-3
Publication status	Published - 11 Aug 2016

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Cite this

Heinzmann, K., Honess, D. J., Lewis, D. Y., Smith, D.-M., Cawthorne, C., Keen, H., Heskamp, S., Schelhaas, S., Witney, T. H., Soloviev, D., Williams, K. J., Jacobs, A. H., Aboagye, E. O., Griffiths, J. R., & 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). https://doi.org/10.1186/s13550-016-0218-3

@article{a5a9cd07ebd44f15ba7e18f7c1fd11ef,

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

abstract = "BackgroundRecent 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.ResultsThe 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.ConclusionsEndogenous tumour thymidine concentrations alone are not predictive of [18F]FLT uptake in murine cancer models.",

author = "K. Heinzmann and D.J. Honess and D.Y. Lewis and D.-M. Smith and C. Cawthorne and H. Keen and S. Heskamp and S. Schelhaas and Witney, {Timothy Howard} and D. Soloviev and K.J. Williams and A.H. Jacobs and E.O. Aboagye and J.R. Griffiths and K.M. Brindle",

year = "2016",

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doi = "10.1186/s13550-016-0218-3",

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journal = "EJNMMI Research",

issn = "2191-219X",

publisher = "BioMed Central",

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Heinzmann, K, Honess, DJ, Lewis, DY, Smith, D-M, Cawthorne, C, Keen, H, Heskamp, S, Schelhaas, S, Witney, TH, Soloviev, D, Williams, KJ, Jacobs, AH, Aboagye, EO, Griffiths, JR & Brindle, KM 2016, 'The relationship between endogenous thymidine concentrations and [¹⁸F]FLT uptake in a range of preclinical tumour models', EJNMMI Research, vol. 6, no. 1. https://doi.org/10.1186/s13550-016-0218-3

TY - JOUR

T1 - The relationship between endogenous thymidine concentrations and [18F]FLT uptake in a range of preclinical tumour models

AU - Heinzmann, K.

AU - Honess, D.J.

AU - Lewis, D.Y.

AU - Smith, D.-M.

AU - Cawthorne, C.

AU - Keen, H.

AU - Heskamp, S.

AU - Schelhaas, S.

AU - Witney, Timothy Howard

AU - Soloviev, D.

AU - Williams, K.J.

AU - Jacobs, A.H.

AU - Aboagye, E.O.

AU - Griffiths, J.R.

AU - Brindle, K.M.

PY - 2016/8/11

Y1 - 2016/8/11

N2 - BackgroundRecent 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.ResultsThe 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.ConclusionsEndogenous tumour thymidine concentrations alone are not predictive of [18F]FLT uptake in murine cancer models.

AB - BackgroundRecent 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.ResultsThe 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.ConclusionsEndogenous tumour thymidine concentrations alone are not predictive of [18F]FLT uptake in murine cancer models.

U2 - 10.1186/s13550-016-0218-3

DO - 10.1186/s13550-016-0218-3

M3 - Article

SN - 2191-219X

VL - 6

JO - EJNMMI Research

JF - EJNMMI Research

IS - 1

ER -