Radiofluorinated N-Octanoyl Dopamine ([18F]F-NOD) as a Tool To Study Tissue Distribution and Elimination of NOD in Vitro and in Vivo.
Radiofluorinated N-Octanoyl Dopamine ([18F]F-NOD) as a Tool To Study Tissue Distribution and Elimination of NOD in Vitro and in Vivo.
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DOI：
10.1021/acs.jmedchem.6b01191
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发表时间：
2016-10
影响因子：
7.3
通讯作者：
M. Pretze;P. Pallavi;M. Roscher;S. Klotz;Julio Caballero;U. Binzen;W. Greffrath;R. Treede;M. Harmsen;M. Hafner;B. Yard;C. Wängler;B. Wängler
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作者：
M. Pretze;P. Pallavi;M. Roscher;S. Klotz;Julio Caballero;U. Binzen;W. Greffrath;R. Treede;M. Harmsen;M. Hafner;B. Yard;C. Wängler;B. Wängler
为了减轻潜在供体器官的移植前损伤，可以考虑N-辛酰多巴胺（NOD）治疗，因为它不影响脑死亡（BD）供体的血流动力学参数。为了更好地评估供体治疗的最佳NOD浓度，我们报告了NOD衍生物[18 F]F-NOD [18 F]5的快速和简便的放射性同位素标记，用于通过PET成像体内评估NOD的消除动力学。[18 F]5的合成具有可重复的高放射化学产率和纯度（>98%）以及高比活度（>20 GBq/μmol）。稳定性试验表明，在大鼠血浆中，[18 F]5在120 min内没有分解。在体外，发现[18 F]5的细胞缔合性较低，表明没有进入细胞的主动转运机制。在体内，[18 F]5表现出快速的血液清除和主要的肝胆消除。由于这些数据表明NOD也可能被快速清除，因此有必要进行进一步的药代动力学评价。
To mitigate pretransplantation injury in organs of potential donors, N-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in braindead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [18F]F-NOD [18F]5 for in vivo assessment of NOD's elimination kinetics by means of PET imaging. [18F]5 was synthesized in reproducibly high radiochemical yields and purity (>98%) as well as high specific activities (>20 GBq/μmol). Stability tests showed no decomposition of [18F]5 over a period of 120 min in rat plasma. In vitro, low cell association was found for [18F]5, indicating no active transport mechanism into cells. In vivo, [18F]5 exhibited a fast blood clearance and a predominant hepatobiliary elimination. As these data suggest that also NOD might be cleared fast, further pharmacokinetic evaluation is warranted.