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Quantification of adenosine A2A receptors in the human brain using [11C]TMSX and positron emission tomography

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

[7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX) is a positron-emitting adenosine A2A receptor (A2AR) antagonist for visualisation of A2AR distribution by positron emission tomography (PET). The aims of this paper were to use a kinetic model to analyse the behaviour of [11C]TMSX in the brain and to examine the applicability of the Logan plot. We also studied the applicability of a simplified Logan plot by omitting metabolite correction and arterial blood sampling.

Methods

The centrum semiovale was used as a reference region on the basis of a post-mortem study showing that it has a negligibly low density of A2ARs. Compartmental analysis was performed in five normal subjects. Parametric images of A2AR binding potential (BP) were also generated using a Logan plot with or without metabolite correction and with or without arterial blood sampling. To omit arterial blood sampling, we applied a method to extract the plasma-related information using independent component analysis (EPICA).

Results

The estimated K 1/k 2 was confirmed to be common in the centrum semiovale and main cortices. The three-compartment model was well fitted to the other regions using the fixed value of K 1/k 2 estimated from the centrum semiovale. The estimated BPs using the Logan plot matched those derived from compartment analysis. Without the metabolite correction, the estimate of BP underestimated the true value by 5%. The estimated BPs agreed regardless of arterial blood sampling.

Conclusion

A three-compartment model with a reference region, the centrum semiovale, describes the kinetic behaviour of [11C]TMSX PET images. A2ARs in the human brain can be visualised as a BP image using [11C]TMSX PET without arterial blood sampling.

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research, No. 16390348 in 2004-2006, No. 18591373 in 2006-2007 and No. 18-6916 in 2006-2008 from the Japan Society for the Promotion of Science, and a Grant-in-Aid for the 21st Century COE from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Naka, Itabashi, Tokyo, 173-0022, Japan

    Mika Naganawa, Yuichi Kimura, Keiichi Oda, Kenji Ishii & Kiichi Ishiwata

  2. Japan Society for the Promotion of Science, Tokyo, Japan

    Mika Naganawa

  3. Neurological Institute, Nippon Medical School Chiba-Hokusoh Hospital, Chiba, Japan

    Masahiro Mishina

  4. Graduate School of Information Science, Nara Institute of Science and Technology, Nara, Japan

    Yoshitsugu Manabe & Kunihiro Chihara

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  1. Mika Naganawa
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  2. Yuichi Kimura
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  3. Masahiro Mishina
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  4. Yoshitsugu Manabe
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  7. Kenji Ishii
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Correspondence to Yuichi Kimura.

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Naganawa, M., Kimura, Y., Mishina, M. et al. Quantification of adenosine A2A receptors in the human brain using [11C]TMSX and positron emission tomography. Eur J Nucl Med Mol Imaging 34, 679–687 (2007). https://doi.org/10.1007/s00259-006-0294-0

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  • DOI: https://doi.org/10.1007/s00259-006-0294-0

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