Application of highly sensitive UPLC-MS to determine biodistribution at tracer doses: validation with the 5-HT1A ligand [18F]FPWAY
Application of highly sensitive UPLC-MS to determine biodistribution at tracer doses: validation with the 5-HT1A ligand [18F]FPWAY
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DOI：
10.1016/j.nucmedbio.2009.01.002
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发表时间：
2009-05-01
影响因子：
3.1
通讯作者：
Kiesewetter, Dale O.
中科院分区：
文献类型：
--
作者：
Ma, Ying;Lang, Lixin;Kiesewetter, Dale O.
高灵敏度和高分辨率的LC/MS仪器已被应用于正电子发射断层扫描（PET）放射色谱法的发展，以提供定量测量的质量的放射性示踪剂提取的大鼠组织。我们采用高灵敏度的沃茨Q-TOF premier MS与Acquity UPLC系统耦合，以证明LC-MS调用生成PET 5-HT 1A配体FPWAY的离体生物分布数据，而无需放射性标记。对于生物分布研究，我们向大鼠注射了含有不同量非放射性FPWAY的[F-18] FPWAY。在规定的时间结束时，处死动物，处理来自每只动物的六个脑区域和血浆，用于通过LC-MS定量测量母体化合物浓度。然后将这些数据转化为微分摄取比DUR（% 1D/g* 体重/100）和脑组织特异性结合率，以允许与通过共注射放射性[F-100]的γ计数获得的数据进行直接比较。[18]FPWAY.使用LC-MS方法计算的DUR和脑组织特异性结合率与通过[F-18] FPWAY的标准放射性测量获得的值高度相关。结论：LC/MS法和放射性法测定DUR和大鼠脑组织特异性结合率具有显著一致性。这种一致性表明，高灵敏度，LC/MS是一个不可或缺的工具，在评估组织中的管理化学品的量作为新的分子成像探针的开发的一部分。爱思唯尔公司出版
High-sensitivity and high-resolution LC/MS instrumentation has been applied in positron emission tomography (PET) radiophrmaceutical development to provide quantitative measurement of the mass of radiotracers extracted from tissues of rats. We employed the highly sensitive Waters Q-TOF premier MS coupled with an Acquity UPLC system to demonstrate that LC-MS call generate ex vivo biodistribution data for PET 5-HT1A ligand FPWAY without the need to radiolabel. For the biodistribution Studies, we injected rats with [F-18] FPWAY containing various amounts of nonradioactive FPWAY. At the end of the allotted time, the animals were killed and six regions of brain and plasma from each animal were processed for quantitative measurement of parent compound concentration by LC-MS. These data were then converted to the differential uptake ratio DUR (%1D/g*body weight/100) and the brain tissue-specific binding ratio to allow direct comparison with data obtained by gamma counting of the coinjected radioactive [F-18]FPWAY. The DUR and the brain tissue-specific binding ratio calculated using the LC-MS method were highly correlated to the values obtained by standard radioactivity measurements of [F-18] FPWAY. In conclusion, there was significant concordance between the LC/MS and radioactivity method in determination of DUR and the specific binding ratio in the rat brain. This concordance indicated that high-sensitivity, LC/MS is an indispensable tool in evaluating the quantity of administered chemical in tissue as part of the development of new molecular imaging probes. Published by Elsevier Inc.