The relationship between endogenous thymidine concentrations and [(18)F]FLT uptake in a range of preclinical tumour models.
The relationship between endogenous thymidine concentrations and [(18)F]FLT uptake in a range of preclinical tumour models.
复制标题
DOI：
10.1186/s13550-016-0218-3
复制
发表时间：
2016-12
期刊：
影响因子：
3.2
通讯作者：
Brindle KM
中科院分区：
文献类型：
--
作者：
Heinzmann K;Honess DJ;Lewis DY;Smith DM;Cawthorne C;Keen H;Heskamp S;Schelhaas S;Witney TH;Soloviev D;Williams KJ;Jacobs AH;Aboagye EO;Griffiths JR;Brindle KM
最近的研究表明，3′-脱氧-3 ′-[18 F]氟胸苷（[18 F]FLT）摄取取决于内源性肿瘤胸苷浓度。本研究的目的是研究肿瘤胸苷浓度以及它们是否与广谱小鼠癌症模型中的[18 F]FLT摄取相关。采用改良的液相色谱-质谱（LC-MS/MS）法测定荷瘤和非荷瘤小鼠和大鼠血浆和组织中的内源性胸苷浓度。在来自6个研究中心的22个肿瘤模型（包括异种移植瘤、同基因和自发性肿瘤）中测定胸苷浓度，并比较一个亚组的[18 F]FLT摄取，通过最大和平均肿瘤-肝脏摄取比（TTL）和SUV进行描述。对用于测定血浆和组织中胸苷的LC-MS/MS方法进行了修改，以提高灵敏度和重现性。7种小鼠品系和1种大鼠品系血浆中测定的胸苷浓度在0.61 ± 0.12 μM和2.04 ± 0.64 μM之间，而22种肿瘤模型中的浓度范围为0.54 ± 0.17 μM至20.65 ± 3.65 μM。在22个肿瘤模型中的14个模型中测定的[18F]FLT注射后60分钟的TTL范围为最大值1.07 ± 0.16至5.22 ± 0.83，平均摄取为0.67 ± 0.17至2.10 ± 0.18。TTL与肿瘤胸苷浓度无关。内源性肿瘤胸苷浓度单独不能预测小鼠癌症模型中的[18 F]FLT摄取。本文的在线版本（doi：10.1186/s13550-016-0218-3）包含补充材料，可供授权用户使用。
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. 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. Endogenous tumour thymidine concentrations alone are not predictive of [18F]FLT uptake in murine cancer models. The online version of this article (doi:10.1186/s13550-016-0218-3) contains supplementary material, which is available to authorized users.