Synthesis and preliminary evaluation of [3H]PSB-0413, a selective antagonist radioligand for platelet P2Y12 receptors

The selective antagonist radioligand [3H]2-propylthioadenosine-5′-adenylic acid (1,1-dichloro-1-phosphonomethyl-1-phosphonyl) anhydride ([3H]PSB-0413) was prepared by catalytic hydrogenation of its propargyl precursor with a high specific radioactivity of 74 Ci/mmol. In preliminary saturation binding studies, [3H]PSB-0413 showed high affinity for platelet P2Y12 receptors with a KD value of 4.57 nM. Human platelets had a high density of P2Y12 receptors exhibiting a Bmax value of 7.66 pmol/mg of protein.