Comparison of three high affinity SPECT radiotracers for the dopamine D₂ receptor

The regional brain distribution and pharmacological specificity of three high affinity tracers for the dopamine (DA) D₂ receptor: [¹²³I]IBF, [¹²³I]epidepride, and [¹²³I]2′-ISP were assessed by SPECT imaging of non-human primates. The ratios of striatal-to-occipital activities at the time of peak striatal uptake were 2.2, 6.3 and 1.7, respectively. From the peak striatal activities, washout rates were 33, 4 and 16%/h for [¹²³I]IBF, [¹²³I]epidepride and [¹²³I]2′-ISP, respectively. The reversibility of the striatal uptake of all three agents was demonstrated by the rapid displacement induced by the dopamine D₂ selective antipsychotic agent raclopride, which increased washout rates to 96, 58 and 43%/h. The administration of d-amphetamine, which induces release of dopamine, had no noticeable effect on [¹²³I]epidepride but increased the washout rate of [¹²³I]IBF. These results suggest that, among these three agents, [¹²³I]epidepride is the superior tracer for in vivo displacement studies because of its slow washout and high target-to-background ratios. However, for tracer kinetic modeling, [¹²³I]IBF may be the superior agent because of its early time of peak uptake and its higher target-to-background ratios than [¹²³I]2′-ISP.