Estimating the effect of endogenous dopamine on baseline [11C]‐(+)‐PHNO binding in the human brain

Endogenous dopamine (DA) levels at dopamine D_2/3 receptors (D_2/3R) have been quantified in the living human brain using the agonist radiotracer [¹¹C]‐(+)‐PHNO. As an agonist radiotracer, [¹¹C]‐(+)‐PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [¹¹C]‐(+)‐PHNO binding to D_2/3Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BP_ND) and the change in BP_ND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [¹¹C]‐(+)‐PHNO BP_ND that can be accounted for by variation in endogenous DA levels across the striatal subregions ranged from 42‐59%. These results indicate that lower baseline values of [¹¹C]‐(+)‐PHNO BP_ND reflect greater stimulation by endogenous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D_2/3R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [¹¹C]‐(+)‐PHNO can detect the impact of endogenous DA levels at D_2/3R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers.