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

Heinzmann, K. et al. (2016) The relationship between endogenous thymidine concentrations and [18F]FLT uptake in a range of preclinical tumour models. EJNMMI Research, 6(1), 63. (doi: 10.1186/s13550-016-0218-3) (PMID:27515446) (PMCID:PMC4980847)

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.

• Item Type: Articles
• Additional Information: The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under grant agreement number 115151, resources of which are composed of a financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. Further information on the QuIC-ConCePT participants is given in the Electronic Supplementary Material. This work was also supported by Cancer Research UK (Grant 17242 to KMB and the CRUK-EPSRC Imaging Centre in Cambridge and Manchester (KMB PI, KJW Co-I; reference 16465) and grant A11562 to JRG.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lewis, Dr David
• Authors: 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., and Brindle, K. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: EJNMMI Research
• Publisher: SpringerOpen
• ISSN: 2191-219X
• ISSN (Online): 2191-219X
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in EJNMMI Research 6(1):63
• Publisher Policy: Reproduced under a Creative Commons License