Kuwabara H, Cumming P, Reith J, Léger G, Diksic M, Evans A C, Gjedde A
Positron Imaging Laboratories, McConnell Brain Imaging Center, Montreal Neurological Institute, Quebec, Canada.
J Cereb Blood Flow Metab. 1993 Jan;13(1):43-56. doi: 10.1038/jcbfm.1993.7.
DOPA decarboxylase is the enzyme directly responsible for the synthesis of the neurotransmitters dopamine and serotonin, and indirectly of noradrenaline, in brain. We used the decarboxylation coefficient (k3D) of 6-[18F]fluoro-DOPA (FDOPA) to denote the relative activity of L-DOPA decarboxylase in vivo in the human brain. To determine the relative enzyme activity with positron emission tomography (PET), we evaluated the model that separates the metabolism into compartments of nondiffusible and diffusible (i.e., transient) tracer metabolites. Error analysis indicated that the least-squares optimization alone was not sufficient to yield accurate estimates of k3D in the presence of the inherent error of PET. To improve the accuracy of the k3D estimates by optimizing the number of parameters, we introduced biological constraints which included a tracer partition volume (Ve) common to frontal cortex and striatum, and a fixed ratio (q) between the blood-brain barrier transport coefficients of O-methyl-[18F]fluoro-DOPA and FDOPA, the two sources of radioactivity in plasma. We found that a two-step analysis yielded sufficiently accurate estimates of k3D. The two steps include the initial estimation of the partition volume in frontal cortex and the subsequent use of this value to determine k3D in striatum and other structures. We studied twelve healthy controls (age 45 +/- 15 years). The average k3D value was 0.081 +/- 0.024 min-1 (coefficient of variation (COV) 30%) for caudate nucleus, 0.074 +/- 0.013 min-1 (COV 18%) for putamen, and 0.010 +/- 0.005 min-1 (COV 50%) for cerebral cortex.
多巴脱羧酶是直接负责在大脑中合成神经递质多巴胺和血清素、间接合成去甲肾上腺素的酶。我们使用6-[18F]氟多巴（FDOPA）的脱羧系数（k3D）来表示人脑中L-多巴脱羧酶的体内相对活性。为了用正电子发射断层扫描（PET）确定相对酶活性，我们评估了将代谢分为不可扩散和可扩散（即瞬时）示踪剂代谢物隔室的模型。误差分析表明，在存在PET固有误差的情况下，仅最小二乘优化不足以产生k3D的准确估计值。为了通过优化参数数量来提高k3D估计的准确性，我们引入了生物学约束，包括额叶皮质和纹状体共有的示踪剂分配体积（Ve），以及血浆中两种放射性来源O-甲基-[18F]氟多巴和FDOPA的血脑屏障转运系数之间的固定比率（q）。我们发现两步分析产生了足够准确的k3D估计值。这两步包括额叶皮质中分配体积的初始估计，以及随后使用该值来确定纹状体和其他结构中的k3D。我们研究了12名健康对照者（年龄45±15岁）。尾状核的平均k3D值为0.081±0.024 min-1（变异系数（COV）30%），壳核为0.074±0.013 min-1（COV 18%），大脑皮质为0.010±0.005 min-1（COV 50%）。
