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.-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), 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
• 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
• Contract Date: Aug 10, 2018