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Ishiwata, K. et al.

Ishiwata, Kawamura, Kimura, Oda, Ishii,

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

In previous in 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 receptor-mediated 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.[1]

References

Potential of an adenosine A2A receptor antagonist [11C]TMSX for myocardial imaging by positron emission tomography: a first human study. Ishiwata, K., Kawamura, K., Kimura, Y., Oda, K., Ishii, K. Annals of nuclear medicine. (2003) [Pubmed]

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