Age-related decline in dopamine transporter in human brain using PET with a new radioligand [ 18 F]FE-PE2I
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ORIGINAL ARTICLE
Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I Yoshitoshi Shingai • Amane Tateno • Ryosuke Arakawa • Takeshi Sakayori • WooChan Kim • Hidenori Suzuki • Yoshiro Okubo
Received: 26 September 2013 / Accepted: 9 December 2013 Ó The Japanese Society of Nuclear Medicine 2013
Abstract Objective 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 [18F]FE-PE2I, a new PET radioligand with high affinity and selectivity for DAT. Methods Thirty-six healthy volunteers ranging in age from 22 to 80 years were scanned with PET employing [18F]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 Y. Shingai A. Tateno R. Arakawa T. Sakayori W. Kim Y. Okubo (&) Department of Neuropsychiatry, Nippon Medical School, Sendagi 1-1-5, Bunkyo-ku, Tokyo 113-8602, Japan e-mail: [email protected] R. Arakawa Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan H. Suzuki Department of Pharmacology, Nippon Medical School, Tokyo, Japan
to age using simple regression analysis. Estimates of DAT loss per decade were obtained using the values from the regression slopes. Results 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. Conclusions [18F]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. Keywords [18F]FE-PE2I Human Positron emission tomography (PET) Dopamine transporter (DAT) Aging
Introduction Dopamine transporter (DAT) plays a crucial role in the regulation of dopamine concentration in the synaptic cleft by dopamine reuptake, and its density is considered as a marker of pre-synaptic function. Changes in the density and function of DAT in living human brain have been reported in studies of various neuropsychiatric disorders using PET, such as Parkinson’s disease (PD) [
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