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Potential of an adenosine A2A receptor antagonist [11C]TMSX for myocardial imaging by positron emission tomography: a first human study

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Abstract

In previousin vivo studies with mice, rats, cats and monkeys, we have demonstrated that [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX) is a potential radioligand for mapping adenosine A2A receptors of the brain by positron emission tomography (PET). In the present study, we studied the potential of [11C]TMSX for myocardial imaging. Uptake of radioactivity by the heart was high and gradually decreased after an intravenous injection of [11C]TMSX into mice. In metabolite analysis, 54% and 76% of the radioactivity in plasma and heart, respectively, were present as the unchanged form of [11C]TMSX 60 min postinjection. The myocardial uptake was reduced by carrier-loading and by co-injection of an adenosine A2A antagonist CSC, but not by co-injection of an adenosine A1 antagonist DPCPX. Pretreatment with a high dose of a non-selective antagonist theophylline also reduced the myocardial uptake of [11C]TMSX. These findings demonstrate the specific binding of [11C]TMSX to adenosine A2A receptors in the heart. Finally we successfully performed the myocardial imaging by PET with [11C]TMSX in a normal volunteer. A graphical analysis by Logan plot supported the receptormediated uptake of [11C]TMSX. Peripherally [11C]TMSX was very stable in human: >90% of the radioactivity in plasma was detected as the unchanged form in a 60-min study. We concluded that [11C]TMSX PET has the potential for myocardial imaging.

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Authors and Affiliations

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

    Kiichi Ishiwata, Kazunori Kawamura, Yuichi Kimura, Keiichi Oda & Kenji Ishii

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  1. Kiichi Ishiwata
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  2. Kazunori Kawamura
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  3. Yuichi Kimura
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  4. Keiichi Oda
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  5. Kenji Ishii
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Correspondence to Kiichi Ishiwata.

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Ishiwata, K., Kawamura, K., Kimura, Y. et al. Potential of an adenosine A2A receptor antagonist [11C]TMSX for myocardial imaging by positron emission tomography: a first human study. Ann Nucl Med 17, 457–462 (2003). https://doi.org/10.1007/BF03006434

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  • DOI: https://doi.org/10.1007/BF03006434

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