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.
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan. ishiwata@pet.tmig.or.jp
Kiichi
K
Ishiwata
Kazunori
K
Kawamura
Yuichi
Y
Kimura
Keiichi
K
Oda
Kenji
K
Ishii
D058917:Adenosine A2 Receptor Antagonists; D000328:Adult; D000818:Animals; D005240:Feasibility Studies; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010865:Pilot Projects; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D014970:Xanthines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; C405422:KF18446; D019275:Radiopharmaceuticals; D043705:Receptor, Adenosine A2A; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine