Imaging the Dopamine D₃ Receptor In Vivo

The dopamine D₃ receptor has been recognized as a distinct entity from the molecularly similar dopamine D₂ receptor, functionally and in anatomical distribution, since 1990, but has not been amenable to characterization of its in vivo properties with imaging techniques for most of that time due to the absence of selective radiotracers. The positron emission tomography radiotracer [¹¹C]-(+)-PHNO, originally developed in 2005 for its D₂/D₃ agonist properties, has recently been shown to be a strongly D₃-preferring tracer that nonetheless binds nontrivially to D₂ receptors as well. While the selectivity properties of this tracer present methodological challenges for pharmacokinetic quantification, [¹¹C]-(+)-PHNO imaging has, for the first time, made D₃ receptor imaging in the living human brain possible, and several interesting results in neuropsychiatric populations have already begun to emerge. In this chapter, we review the methodological developments of D₃ receptor imaging with [¹¹C]-(+)-PHNO in both preclinical species and humans, as well as imaging studies that have been performed in patient populations.