Improved detection and measurement of low levels of [18F]fluoride metabolized from [18F]-labeled pyrimidine nucleoside analogues in biological samples
Improved detection and measurement of low levels of [18F]fluoride metabolized from [18F]-labeled pyrimidine nucleoside analogues in biological samples
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DOI：
10.1016/j.nucmedbio.2011.05.008
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发表时间：
2011-11-01
影响因子：
3.1
通讯作者：
Alauddin, Mian M.
中科院分区：
文献类型：
--
作者：
Paolillo, Vincenzo;Yeh, Hsin Hsien;Alauddin, Mian M.
前言：对[F-18]标记的放射性示踪剂进行准确的药代动力学建模，重要的是要确定所有循环代谢物，包括游离氟。我们试图确定最有效的方法来检测和定量生物样品中低水平的游离[F-18]氟。方法：使用两种方法对低水平的[F-18]氟进行分析：(A)离子交换色谱柱和伽马计数法，以及(B)放射高效液相色谱法，比较这两种分析方法的检出限。将20微升的[F-18]氟化物溶液装载到离子交换柱上，然后用20%的MeCN/水(5毫升)洗脱，并用伽马计数器计数捕获在柱内的放射性。[F-18]标记胸腺嘧啶核苷类似物注射小鼠的血浆和尿液中的氟也用A方法测定。结果：A方法的检测灵敏度是B方法的9.4倍(0.075+/-0.004对0.71+/-0.02nCI)。[F-18]FMAU、[F-18]FeAu和N-3-[F-18]FPRT的血浆氟含量分别为1.4+/-0.31%(n=4)、0.17+/-0.49%(n=3)、4.88+/-1.62%(n=3)和12.94+/-0.48%(n=4)。尿氟测定值分别为11.49+/-1.60%(n=4)和5.36+/-2.34%(n=3)。来自[F-18]FeAU的13.57+/-1.96%(n=3)和来自N-3-[F-18]FPrT的11.19+/-1.98%(n=4)。结论：使用离子交换盒和伽马计数法可以检测和定量生物样品中的低水平的[F-18]氟。该方法简单、准确，优于在C-18色谱柱上进行代谢物分析的标准使用的放射性高效液相色谱，在使用[F-18]标记的放射性示踪剂和PET进行动物成像研究的药代动力学建模中应该是有用的。(C)2011 Elsevier Inc.保留所有权利。
Introduction: It is important to identify all circulating metabolites, including free fluoride, for accurate pharmacokinetic modeling of [F-18]-labeled radiotracers. We sought to determine the most efficient method to detect and quantify low levels of free [F-18]fluoride in biological samples.Methods: Low levels of [F-18]fluoride were analyzed using two methods: (A) an ion-exchange cartridge and gamma counting, and (B) radio-HPLC, to compare the detection limits of these two analytical methods. Twenty microliters of [F-18]fluoride solution was loaded onto an ion-exchange cartridge, then eluted with 20% MeCN/water (5 ml) and radioactivity trapped in the cartridge counted on a gamma counter. [F-18] Fluoride was also determined in plasma and urine from mice injected with [F-18]-labeled thymidine analogues using Method A.Results: The detection sensitivity of Method A was 9.4-fold higher than that of Method B (0.075 +/- 0.004 vs. 0.71 +/- 0.02 nCi). With Method A, [F-18]fluoride was determined in plasma for [F-18]FLT, [F-18]FMAU, [F-18]FEAU and N-3-[F-18]FPrT as 1.4 +/- 0.31% (n=4), 0.17 +/- 0.49% (n=3), 4.88 +/- 1.62% (n=3) and 12.94 +/- 0.48% (n=4), respectively. The amount of [F-18]fluoride determined in the urine was 11.49 +/- 1.60% (n=4) from [F-18]FLT, 5.36 +/- 2.34% (n=3) from [F-18]FMAU, 13.57 +/- 1.96% (n=3) from [F-18]FEAU and 11.19 +/- 1.98% (n=4) from N-3-[F-18]FPrT.Conclusion: Low levels of [F-18]fluoride in biological samples can be detected and quantified using an ion-exchange cartridge and gamma counting. This methodology is simple, accurate and superior to the standard use of radio-HPLC on a C-18 column for metabolite analysis, and it should be useful in pharmacokinetic modeling for animal imaging studies using an [F-18]-labeled radiotracer and PET. (C) 2011 Elsevier Inc. All rights reserved.