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Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I

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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 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.

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Acknowledgments

The authors thank Dr. Kiichi Ishiwata (Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan) and Dr. Shinji Kageyama (Mitsubishi Chemical Medience Corp., Tokyo, Japan), Mr. Koji Nagaya, Mr. Koji Kanaya, Mr. Masaya Suda, Ms. Megumi Takei, Mr. Kazuyoshi Honjo, and Mr. Minoru Sakurai (Clinical Imaging Center for Healthcare, Nippon Medical School, Tokyo, Japan) for their assistance with this study. This work was partially supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT, Japan). Dr. Suzuki has received speaker’s honoraria from Pfizer and Eisai within the past 3 years. Dr. Okubo has received grants or speaker’s honoraria from Dainippon Sumitomo Pharma, GlaxoSmithKline, Janssen Pharmaceutical, Otsuka, Pfizer, Eli Lilly, Astellas, Yoshitomi and Meiji within the past 3 years. For the remaining authors none were declared.

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Correspondence to Yoshiro Okubo.

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Shingai, Y., Tateno, A., Arakawa, R. et al. Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I. Ann Nucl Med 28, 220–226 (2014). https://doi.org/10.1007/s12149-013-0798-1

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  • DOI: https://doi.org/10.1007/s12149-013-0798-1

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