Loss of metabolites from monkey striatum during PET with FDOPA
Loss of metabolites from monkey striatum during PET with FDOPA
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DOI：
10.1002/syn.1077
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发表时间：
2001-09-01
期刊：
影响因子：
2.3
通讯作者：
Doudet, D
中科院分区：
文献类型：
--
作者：
Cumming, P;Munk, OL;Doudet, D
6-[F-18]氟多巴（FDOPA）的脱羧作用和产物[F-18]氟多巴在儿茶酚胺纤维囊泡内的保留导致FDOPA/PET研究期间多巴胺富集脑区域的标记。然而，由于[F-18]氟多巴代谢物最终从脑中扩散，这种代谢捕获不是不可逆的。因此，纹状体的时间放射性记录逐渐受到代谢物损失的影响。在线性分析中，FDOPA的净血脑清除率（Ki（D），ml g（-1）min（-1））可以通过消除速率常数k（cl）（Lin）（min（-1））针对该损失进行校正。同样，。通过隔室分析计算的DOPA脱羧速率常数（k（3）（D），min（-1））也可以通过消除速率常数k（9）（DA）（min（-1））校正代谢物损失。为了比较这两种方法，我们使用在正常猴和单侧1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）损伤的猴中FDOPA循环240分钟期间记录的数据计算两种消除速率常数。扩展模型的使用增加了纹状体中Ki（D）和k（3）（D）的幅度;在k（3）（D）的情况下，在校正代谢物损失后，估计的方差得到了实质性改善。代谢产物损失的速率常数在MPTP损伤的猴纹状体比正常纹状体更高。k（cl）（Lin）和k（9）（DA）的个体估计值之间的高度相关性表明，这两个速率常数均表明大脑中脱羧代谢物的损失。Synapse 41：212-218，2001. (C)2001 Wiley-Liss，Inc.
The decarboxylation of 6-[F-18]fluorodopa (FDOPA) and retention of the product [F-18]fluorodopamine within vesicles of catecholamine fibers results in the labeling of dopamine-rich brain regions during FDOPA/PET studies. However, this metabolic trapping is not irreversible due to the eventual diffusion of [F-18]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K-i(D), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate constant k(cl)(Lin) (min(-1)). Similarly,. the DOPA decarboxylation rate constant (k(3)(D), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(9)(DA) (min(-1)). To compare the two methods, we calculated the two elimination rate, constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K-i(D) and k(3)(D) in striatum; in the case of k(3)(D), variance of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(cl)(Lin) and k(9)(DA) suggests that both rate constants reveal loss of decarboxylated metabolites from brain. Synapse 41:212-218, 2001. (C) 2001 Wiley-Liss, Inc.