Distribution kinetics of 18F-DOPA in weaver mutant mice

Sushil K. Sharma, Manuchair Ebadi
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引用次数: 23

Abstract

Distribution kinetics of 18F-fluoro-dihydroxy phenylalanine (18F-DOPA) were studied with high-resolution micro-positron emission tomography (microPET) imaging and conventional methods in control wild-type mice, heterozygous weaver mutant mice, and homozygous weaver mutant mice. 18F-DOPA uptake was significantly increased in the CNS within 60 min in all the genotypes examined. Homozygous weaver mutant mice exhibited significantly reduced 18F-DOPA uptake in the region of interest (striatum) as compared to heterozygous weaver mutant mice and control wild-type mice. 18F-DOPA was de-localized in the kidneys of homozygous weaver mutant mice. The radioactivity was localized primarily in the liver and kidneys within 2 h and in the urinary bladder within 4 h. After 8 h, it could be detected neither by conventional nor by microPET imaging. Distribution kinetics of 18F-DOPA with microPET imaging correlated and confirmed the conventional observations. These data are interpreted to suggest that microPET imaging may provide an efficient, noninvasive, cost-effective procedure to study distribution kinetics of PET radiopharmaceuticals in rare genetically altered animals. Furthermore, this unique and noninvasive approach may expedite quality control and drug development for human applications.

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18F-DOPA在weaver突变小鼠体内的分布动力学
采用高分辨率微正电子发射断层扫描(microPET)和常规方法研究了18f -氟二羟基苯丙氨酸(18F-DOPA)在对照野生型小鼠、杂合子编织突变小鼠和纯合子编织突变小鼠中的分布动力学。在所有检测的基因型中,60分钟内中枢神经系统的18F-DOPA摄取显著增加。纯合子织布突变小鼠与杂合子织布突变小鼠和对照野生型小鼠相比,在感兴趣区域(纹状体)的18F-DOPA摄取显著减少。18F-DOPA在纯合子weaver突变小鼠的肾脏中去定位。放射性在2小时内主要局限于肝脏和肾脏,4小时内主要局限于膀胱。8小时后,常规和显微pet成像均无法检测到放射性。显微pet成像证实了18F-DOPA的分布动力学。这些数据表明,微PET成像可能为研究PET放射性药物在稀有转基因动物中的分布动力学提供一种有效、无创、经济的方法。此外,这种独特的非侵入性方法可以加快人类应用的质量控制和药物开发。
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