The relationship between endogenous thymidine concentrations and [(18)F]FLT uptake in a range of preclinical tumour models.
EJNMMI Res
; 6(1): 63, 2016 Dec.
Article
em En
| MEDLINE
| ID: mdl-27515446
ABSTRACT
BACKGROUND:
Recent studies have shown that 3'-deoxy-3'-[(18)F] fluorothymidine ([(18)F]FLT)) uptake depends on endogenous tumour thymidine concentration. The purpose of this study was to investigate tumour thymidine concentrations and whether they correlated with [(18)F]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 [(18)F]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 [(18)F]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 [(18)F]FLT uptake in murine cancer models.
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Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
EJNMMI Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Reino Unido