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Quantitative analysis of dopamine transporters in human brain using [11C]PE2I and positron emission tomography: evaluation of reference tissue models

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Abstract

Objective

Dopamine transporter (DAT) is a reuptake carrier of dopamine at presynapse that regulates dopaminergic neural transmission. [11C]PE2I is a cocaine analog developed as a potent positron emission tomography (PET) ligand for DAT with high selectivity. The aim of this study was to evaluate the applicability of quantification methods using reference tissue models for [11C]PE2I.

Methods

Dynamic PET scans were performed in 6 young healthy male volunteers after an intravenous bolus injection of [11C]PE2I. Metabolite-corrected arterial plasma-input functions were obtained. Compartment model analysis and plasma-input Logan analysis were performed to determine the kinetic parameters and distribution volume (V T). The distribution volume ratio (DVR) was calculated as the ratio of V T in the cerebral region to that in the cerebellum. DVRs were also determined by the original multilinear reference tissue model method (MRTMo) and the simplified reference tissue model method (SRTM), comparing the results with those obtained from graphical analysis using arterial input function. To estimate errors in DVR calculated using the reference tissue model, a simulation study that focused on cerebellar kinetics and scan duration was performed.

Results

The highest [11C]PE2I binding was observed in the striatum, followed by the midbrain and thalamus. The 2-tissue model was preferable to the 1-tissue model for describing the [11C]PE2I kinetics in the cerebellum. Both the measured and 90-min simulated data showed that reference tissue models caused an underestimation of DVR in the striatum. The simulation showed that 90-min scan duration was insufficient when cerebellar kinetics was described as a 1-tissue model. Nevertheless, DVR values determined by MRTMo and SRTM were in good agreement with those by the graphical approach in other lower binding regions.

Conclusion

Due to the [11C]PE2I kinetics in the cerebellum and limited scan duration for 11C, MRTMo and SRTM underestimated the striatal DVR. Despite this limitation, the present study demonstrated the applicability of reference tissue models. Since DAT in the midbrain and thalamus is of interest in the pathophysiology of neuropsychiatric disease, this noninvasive quantitative analysis will be useful for clinical investigations.

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Acknowledgments

This study was supported by a consignment expense for the Molecular Imaging Program on “Research Base for PET Diagnosis” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japanese Government. The authors are thankful to Ms. Yoshiko Fukushima for organization of the clinical study and to the staff of the PET facility for their clinical assistance. We are also grateful to Dr. Masanori Ichise for his professional advice regarding the use of MRTMo, Prof. Adriaan A. Lammertsma for his kind assistance with the derivation of SRTM for DVR and to Dr. Mika Naganawa for constructive comments in the preparation of the manuscript.

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  1. Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan

    Chie Seki, Hiroshi Ito, Tetsuya Ichimiya, Ryosuke Arakawa, Yoko Ikoma, Miho Shidahara, Jun Maeda, Akihiro Takano, Hidehiko Takahashi, Yuichi Kimura, Kazutoshi Suzuki, Iwao Kanno & Tetsuya Suhara

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  1. Chie Seki
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Correspondence to Hiroshi Ito.

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Seki, C., Ito, H., Ichimiya, T. et al. Quantitative analysis of dopamine transporters in human brain using [11C]PE2I and positron emission tomography: evaluation of reference tissue models. Ann Nucl Med 24, 249–260 (2010). https://doi.org/10.1007/s12149-010-0364-z

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