Imaging the D3 receptor in humans in vivo using [11C](+)-PHNO positron emission tomography (PET).

Imaging the dopamine D3 receptor (D3R) in humans in vivo has been hampered by the lack of suitable tools. The D3R is pharmacologically similar to the dopamine D2 receptor (D2R), and is located in the same brain areas as the D2R, albeit at significantly lower density. The signal obtained from a positron emission tomography (PET) study is proportional to the target density ( B avail) and the affinity of the PET radioligand for the target ( K d). Existing D2/D3 PET ligands ([11C]raclopride, [11C]FLB457, [18F] and [11C]fallypride, [11C]NPA, [11C]NMSP) have similar affinity for the two sites, and therefore their binding informs about the significantly more abundant D2R, rather than D3R. Despite numerous attempts to develop PET radioligands with significant selectivity for D3R over D2R (Bennacef et al. 2009; Sovago et al. 2005; Xu et al. 2009) no useful ligand has been reported to date. Thus [11C](+)-PHNO introduced by Wilson et al. (2005) as a D2R agonist ligand, provided a pleasant surprise, when preferential affinity …

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