Assessment of Fetal Brain Uptake of Paraquat In Utero Using In Vivo PET/CT Imaging
Assessment of Fetal Brain Uptake of Paraquat In Utero Using In Vivo PET/CT Imaging
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DOI：
10.1093/toxsci/kfr104
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发表时间：
2011-08-01
影响因子：
3.8
通讯作者：
DeJesus, Onofre T.
中科院分区：
文献类型：
--
作者：
Bartlett, Rachel M.;Murali, Dhanabalan;DeJesus, Onofre T.
产前子宫条件被认为在包括帕金森病（PD）在内的成人疾病的发展中发挥作用。百草枯是一种常见的除草剂，其化学结构类似于1-甲基-4-苯基1,2,3,6-四氢吡啶，一种已知可诱发帕金森病的神经毒素。为了评估子宫内百草枯暴露在PD中的作用，使用正电子发射断层扫描(PET)/计算机断层扫描（CT）成像测量了母体和胎儿大脑的摄取。对2只妊娠中后期麻醉的恒河猴静脉注射c -11-百草枯，并进行全身PET/CT成像。以母体心室血池为输入函数，利用Patlak图形分析计算了母体和胎儿大脑中百草枯从血浆到大脑的不可逆运输的单向内流速率常数（K(i)s）。结果表明，母体和胎儿大脑对百草枯的吸收最小，平均K(i)s分别为每分钟0.0009和0.0016。母体大脑中最高的区域脑摄取（注射剂量0.0009%）见于松果体，这是一种已知缺乏血脑屏障的结构。母体和胎儿大脑中微量百草枯摄取的发现与先前在成年雄性猕猴中的发现相似，并扩展了单次急性百草枯暴露（产前或产后）不太可能在PD中起作用的争论。
Prenatal in utero conditions are thought to play a role in the development of adult diseases including Parkinson's disease (PD). Paraquat is a common herbicide with chemical structure similar to 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine, a neurotoxin known to induce parkinsonism. In order to assess the role of in utero paraquat exposure in PD, uptake in maternal and fetal brains were measured using positron emission tomography (PET)/computed tomography (CT) imaging. Two anesthetized pregnant rhesus macaques in the late second trimester of pregnancy were given bolus iv injections of C-11-paraquat, and whole-body PET/CT imaging was performed. Using maternal ventricular blood pool as the input function, the unidirectional influx rate constants (K(i)s), a measure of the irreversible transport of paraquat from plasma to brain, were calculated for the maternal and fetal brains using Patlak graphical analysis. Results indicate minimal uptake of paraquat by both maternal and fetal brains with average K(i)s of 0.0009 and 0.0016 per minute, respectively. The highest regional cerebral uptake in the maternal brain (0.0009% injected dose) was seen in the pineal gland, a structure known to lack a blood brain barrier. The finding of minimal paraquat uptake in maternal and fetal brains is similar to previous findings in adult male macaques and extends the contention that a single acute paraquat exposure, prenatally or postnatally, is unlikely to play a role in PD.