Sharma Sushil K, Ebadi Manuchair
Center of Excellence in Neuroscience, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND 58203, USA.
Brain Res Mol Brain Res. 2005 Sep 13;139(1):23-30. doi: 10.1016/j.molbrainres.2005.05.018.
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.
利用高分辨率微型正电子发射断层扫描（microPET）成像和传统方法，研究了18F-氟二羟基苯丙氨酸（18F-DOPA）在对照野生型小鼠、杂合型weaver突变小鼠和纯合型weaver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（CNS）对18F-DOPA的摄取显著增加。与杂合型weaver突变小鼠和对照野生型小鼠相比，纯合型weaver突变小鼠在感兴趣区域（纹状体）的18F-DOPA摄取显著降低。18F-DOPA在纯合型weaver突变小鼠的肾脏中出现异位分布。放射性在2小时内主要定位于肝脏和肾脏，4小时内定位于膀胱。8小时后，无论是通过传统方法还是microPET成像都无法检测到。18F-DOPA的microPET成像分布动力学与传统观察结果相关并得到证实。这些数据表明，microPET成像可能为研究PET放射性药物在罕见基因改变动物中的分布动力学提供一种高效、无创、经济有效的方法。此外，这种独特的无创方法可能会加快人类应用的质量控制和药物开发。
