Evaluation of [4‐O‐methyl‐11C]KW‐6002 as a potential PET ligand for mapping central adenosine A2A receptors in rats

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Abstract
KW-6002, a xanthine-based adenosine A2A antagonist, was labelled with the positron emitter carbon-11 by O-methylation of its precursor, KF23325, using [11C]iodomethane and was evaluated in rats as a putative in vivo radioligand for positron emission tomography (PET). Following intravenous injection of [11C]KW-6002, radioactivity was measured in blood, plasma, peripheral tissues, and in discrete brain tissues over a 2-h time period commensurate with PET scanning. In brain, [11C]KW-6002 showed highest retention in striata, with evidence of saturable binding, and lowest retention in frontal cortex (a tissue low in adenosine A2A receptors). PET scanning with [11C]KW-6002 demonstrated a specific signal in the striata which could be described using compartmental modelling. Specific binding was, however, also detected in extrastriatal regions, including brain areas reported to have low adenosine A2A receptor density. Blocking studies with the A1 selective antagonist KF15372 and the non xanthine-type A2A antagonist ZM 241385 failed to elucidate the nature of this binding. Thus, although [11C]KW-6002 shows some potential for development as a PET ligand for quantifying striatal adenosine A2A receptor function, its in vivo selectivity requires further investigation. Synapse 42:164–176, 2001.