Shingai Yoshitoshi, Tateno Amane, Arakawa Ryosuke, Sakayori Takeshi, Kim WooChan, Suzuki Hidenori, Okubo Yoshiro
Department of Neuropsychiatry, Nippon Medical School, Sendagi 1-1-5, Bunkyo-ku, Tokyo, 113-8602, Japan.
Ann Nucl Med. 2014 Apr;28(3):220-6. doi: 10.1007/s12149-013-0798-1. Epub 2014 Jan 3.
Dopamine transporter (DAT) density is considered as a marker of pre-synaptic function. Numerous neuroimaging studies have consistently demonstrated an age-related decrease in DAT density in normal human brain. However, the precise degree of the regional decline is not yet clear. The purpose of this study was to evaluate the effect of the normal aging process on DAT densities in human-specific brain regions including the substantia nigra and thalamus using positron emission tomography (PET) with [(18)F]FE-PE2I, a new PET radioligand with high affinity and selectivity for DAT.
Thirty-six healthy volunteers ranging in age from 22 to 80 years were scanned with PET employing [(18)F]FE-PE2I for measuring DAT densities. Region of interest (ROI)-based analysis was used, and ROIs were manually defined for the caudate, putamen, substantia nigra, thalamus, and cerebellar cortex. DAT binding was quantified using a simplified reference tissue model, and the cerebellum was used as reference region. Estimations of binding potential in the caudate, putamen, substantia nigra, and thalamus were individually regressed according to age using simple regression analysis. Estimates of DAT loss per decade were obtained using the values from the regression slopes.
There were 7.6, 7.7, and 3.4% per-decade declines in DAT in the caudate, putamen, and substantia nigra, respectively. By contrast, there was no age-related decline of DAT in the thalamus.
[(18)F]FE-PE2I allowed reliable quantification of DAT, not only in the caudate and putamen but also in the substantia nigra. From the results, we demonstrated the age-related decline in the caudate and putamen as reported in previous studies, and additionally for those in the substantia nigra for the first time.
多巴胺转运体（DAT）密度被视为突触前功能的标志物。众多神经影像学研究一致表明，正常人类大脑中DAT密度会随年龄增长而降低。然而，各区域下降的精确程度尚不清楚。本研究的目的是使用正电子发射断层扫描（PET）和[(18)F]FE-PE2I（一种对DAT具有高亲和力和选择性的新型PET放射性配体）来评估正常衰老过程对包括黑质和丘脑在内的人类特定脑区DAT密度的影响。
对36名年龄在22至80岁之间的健康志愿者进行PET扫描，使用[(18)F]FE-PE2I测量DAT密度。采用基于感兴趣区域（ROI）的分析方法，手动为尾状核、壳核、黑质、丘脑和小脑皮质定义ROI。使用简化参考组织模型对DAT结合进行量化，小脑用作参考区域。使用简单回归分析，根据年龄对尾状核、壳核、黑质和丘脑中结合潜力的估计值进行单独回归。使用回归斜率的值获得每十年DAT损失的估计值。
尾状核、壳核和黑质中DAT每十年分别下降7.6%、7.7%和3.4%。相比之下，丘脑中DAT没有与年龄相关的下降。
[(18)F]FE-PE2I不仅能够可靠地量化尾状核和壳核中的DAT，还能量化黑质中的DAT。根据结果，我们证实了先前研究中报道的尾状核和壳核中与年龄相关的下降情况，并且首次证实了黑质中的下降情况。
