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

Heinzmann, Kathrin; Honess, Davina Jean; Lewis, David Yestin; Smith, Donna-Michelle; Cawthorne, Christopher; Keen, Heather; Heskamp, Sandra; Schelhaas, Sonja; Witney, Timothy Howard; Soloviev, Dmitry; Williams, Kaye Janine; Jacobs, Andreas Hans; Aboagye, Eric Ofori; Griffiths, John Richard; Brindle, Kevin Michael

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.

Citation

Heinzmann, K., Honess, D. J., Lewis, D. Y., Smith, D., Cawthorne, C., Keen, H., …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), Article 63. https://doi.org/10.1186/s13550-016-0218-3

• Journal Article Type: Article
• Acceptance Date: Jul 28, 2016
• Online Publication Date: Aug 11, 2016
• Publication Date: Dec 1, 2016
• Deposit Date: Aug 8, 2018
• Publicly Available Date: Aug 10, 2018
• Journal: EJNMMI Research
• Print ISSN: 2191-219X
• Electronic ISSN: 2191-219X
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 1
• Article Number: 63
• DOI: https://doi.org/10.1186/s13550-016-0218-3
• Keywords: [18F]Fluorothymidine; Plasma; Tumour; Thymidine; Preclinical PET
• Public URL: https://hull-repository.worktribe.com/output/972029
• Publisher URL: https://ejnmmires.springeropen.com/articles/10.1186/s13550-016-0218-3
• Related Public URLs: https://www.repository.cam.ac.uk/handle/1810/260243