Continuous infusion [¹¹C]-(+)-PHNO PET for measuring dopamine D_2/3 receptor availability and amphetamine effects...

Dopamine D_2/3 receptors are expressed throughout the human brain, but synchronous receptor quantification in subcortical and cortical brain areas remains difficult to achieve with a single radioligand. Here, we assessed the suitability of a bolus plus constant infusion (B/I) paradigm for brain-wide dopamine D_2/3 receptor imaging with the agonist radioligand [¹¹C]-(+)-PHNO.

Five healthy male volunteers underwent two B/I [¹¹C]-(+)-PHNO positron emission tomography (PET) scans combined with a mid-scan intravenous amphetamine challenge. Non-displaceable binding potentials (BP_ND) were calculated using the equilibrium ratio method and an algorithmically constrained cerebellum as the reference region.

Reproducible baseline BP_ND values were obtained for the majority of regions examined, with intraclass correlation coefficients ranging from 0.5 to 0.93, and test-retest variability remaining below 10%. Moreover, amphetamine-induced decreases in receptor binding were observed in both scans in cortical and a number of subcortical regions. In the globus pallidus and ventral striatum, however, equilibrium had not been reached prior to amphetamine injection, suggesting that further optimization of the protocol might be needed to quantify amphetamine effects in D₃ receptor-rich regions.

These results indicate that, within certain limitations, synchronous cortical and subcortical measurements of D_2/3 receptors at baseline and under challenge conditions can be achieved using the B/I approach and [¹¹C]-(+)-PHNO PET.