[4- O- methyl-¹¹C]-8-[(E)-2-(3,4-Dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione

Adenosine is an endogenous nucleoside that modulates a number of physiological functions in the central nervous system and in peripheral organs, such as the heart, kidneys, and muscle (1, 2). The effect is mediated by two major subtypes of receptors (A₁ and A_2A) and two minor subtypes (A_2B and A₃). In the central nervous system, A₁ receptors are present both pre- and postsynaptically in the hippocampus, cerebral cortex, thalamus, striatum, and cerebellum. A_2A receptors are highly concentrated and co-localized with dopamine D₁ and D₂ receptors in the striatum, nucleus accumbens, and olfactory tubercle. A_2A receptors are also present in low amounts in the hippocampus and cortex. A_2B receptors are widely distributed, but concentrations are high in the gastrointestinal tract. A₃ receptors are also widely distributed, with high concentrations in testis. A₁ and A₃ receptors mediate inhibition of adenylyl cyclase, whereas A_2A and A_2B receptors mediate stimulation. Changes in the adenosine functions are implicated in epilepsy, ischemic cerebral stroke, movement disorders, sleep disorders, and psychiatric disorders (3-5).

A_2A receptors have been studied in vivo with positron emission tomography (PET) using [7-methyl-¹¹C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([¹¹C]TMSX), a methyl xanthine analog of KF17387 with selective A_2A antagonistic activity (6). [¹¹C]TMSX is being developed as a PET agent for the non-invasive study of A_2A receptors in the human brain. 8-[(E)-2-(3,4-Dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione (KW-6002), another xanthine derivative, is a potent and selective A_2A antagonist with a 50% inhibition concentration (K_i) value of 2.2 nM (7). [4-O-methyl-¹¹C]-KW-6002 ([¹¹C]KW-6002) is being developed as a PET agent for the non-invasive study of A_2A receptors in the human brain (8).