Landvogt Christian, Mengel Eugen, Bartenstein Peter, Buchholz Hans Georg, Schreckenberger Mathias, Siessmeier Thomas, Scheurich Armin, Feldmann Reinhold, Weglage Josef, Cumming Paul, Zepp Fred, Ullrich Kurt
Department of Nuclear Medicine, University of Mainz, Mainz, Germany.
J Cereb Blood Flow Metab. 2008 Apr;28(4):824-31. doi: 10.1038/sj.jcbfm.9600571. Epub 2007 Oct 31.
Deficiency of phenylalanine hydroxylase activity in phenylketonuria (PKU) causes an excess of phenylalanine (Phe) throughout the body, predicting impaired synthesis of catecholamines in the brain. To test this hypothesis, we used positron emission tomography (PET) to measure the utilization of 6-[18F]fluoro-L-DOPA [corrected] (FDOPA) in the brain of adult patients suffering from PKU and in healthy controls. Dynamic 2-h long FDOPA emission recordings were obtained in seven adult PKU patients (five females, two males; age: 21 to 27 years) with elevated serum Phe levels, but lacking neurologic deficits. Seven age-matched, healthy volunteers were imaged under identical conditions. The utilization of FDOPA in striatum was calculated by linear graphical analysis (k3S, min(-1)), with cerebellum serving as a nonbinding reference region. The time to peak activity in all brain time-radioactivity curves was substantially delayed in the PKU patients relative to the control group. The mean magnitude of k3S in the striatum of the PKU patients (0.0052+/-0.0004 min(-1)) was significantly lower than in the control group (0.0088+/-0.0009 min(-1)) (P<0.001). There was no significant correlation between individual serum Phe levels and k3S. The unidirectional clearance of FDOPA to brain was impaired in adult patients suffering from PKU, presumably reflecting the competitive inhibition of the large neutral amino acid carrier by Phe. Assuming this competition to be spatially uniform, the relationship between striatum and cerebellum time-activity curves additionally suggests inhibition of DOPA efflux, possibly also due to competition from Phe. The linear graphical analysis shows reduced k3S in striatum, indicating reduced DOPA decarboxylase activity.
苯丙酮尿症（PKU）中苯丙氨酸羟化酶活性缺乏会导致全身苯丙氨酸（Phe）过量，这预示着大脑中儿茶酚胺的合成受损。为了验证这一假设，我们使用正电子发射断层扫描（PET）来测量成年PKU患者和健康对照者大脑中6-[18F]氟-L-多巴[校正后]（FDOPA）的利用率。在7名血清Phe水平升高但无神经功能缺损的成年PKU患者（5名女性，2名男性；年龄：21至27岁）中获得了长达2小时的动态FDOPA发射记录。7名年龄匹配的健康志愿者在相同条件下进行成像。通过线性图形分析（k3S，min(-1)）计算纹状体中FDOPA的利用率，小脑作为非结合参考区域。与对照组相比，PKU患者所有脑时间-放射性曲线中的峰值活动时间明显延迟。PKU患者纹状体中k3S的平均幅度（0.0052±0.0004 min(-1)）显著低于对照组（0.0088±0.0009 min(-1)）（P<0.001）。个体血清Phe水平与k3S之间无显著相关性。成年PKU患者中FDOPA向大脑的单向清除受损，推测这反映了Phe对大中性氨基酸载体的竞争性抑制。假设这种竞争在空间上是均匀的，纹状体和小脑时间-活动曲线之间的关系还表明DOPA流出受到抑制，这可能也是由于Phe的竞争所致。线性图形分析显示纹状体中k3S降低，表明多巴脱羧酶活性降低。
