Proposal of adenosine receptor ligands as new diagnostic probes for myocaridial function by PET

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As a new diagnostic technique for myocardial functions by positron emission tomography (PET), positron emitting ligands for adenosine receptors and adenosine transporters were prepared and their potential as in vivo probes was evaluated.As adenosine AィイD22AィエD2 receptor ligands, seven xanthine-type compounds were labeled with ィイD111ィエD1C-methyl iodide. In vivo studies with mice and rats shoed that [ィイD111ィエD1C]KF19631 ([7-methyl-ィイD111ィエD1C]-(E)-1,3-diallyl-7-methyl-8-(3,4,5-trimethoxystyryl)xanthine) had the highest affinity for the myocardial adenosine AィイD22AィエD2 receptors. The AィイD22AィエD2 receptors in the heart of rabbits were clearly visualized by PET with [ィイD111ィエD1C]KF19631. In the in vivo blocking study with another ligand [ィイD111ィエD1C]KF17837, it is suggested that the in vivo binding of xanthine-type ligands was different from that of nonxnthine-type ligands. The compounds, which are potentially labeled with radioactive bromine or iodine, were also labeled with ィイD111ィエD1C, b … More ut the receptor-specific uptake by the heart was not found.As an adenosine transporter blocker, [ィイD111ィエD1C]KF21652(3-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl-1,2,3,4-tetrahydro-1-[ィイD111ィエD1C]methyl-6-nitro-2,4-dioxoquinazoline) was prepared. In mice the uptake of [ィイD111ィエD1C]KF21652 by the heart decreased with time, and the transporter-mediated uptake of the compound was not observed in the all organs including the heart and brain. On the other hand, in vitro autoradiography showed the binding of [ィイD111ィエD1C]KF21562 to adenosine transporters, but with a high non-specific binding. These results show that the compound is not a suitable PET ligand for mapping adenosine transporter receptors.We concluded that [ィイD111ィエD1C]KF19631 is a suitable PET ligand for mapping myocardial adenosine AィイD22aィエD2 receptors. The clinical application of this ligand is of great interest to understand the regulation and properties of the adenosine receptors in the normal subjects and patients with cardiovascular disease. Less