TY - JOUR T1 - PET imaging of dopamine D3 receptors in humans with [11C]-(+)-PHNO: Validation using a selective D3 antagonist JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 158 LP - 158 VL - 51 IS - supplement 2 AU - Graham Searle AU - John Beaver AU - Robert Comley AU - Massimo Bani AU - Andri Tziortzi AU - Mark Slifstein AU - Alan Wilson AU - Roger Gunn AU - Eugenii Rabiner AU - Marc Laruelle Y1 - 2010/05/01 UR - http://jnm.snmjournals.org/content/51/supplement_2/158.abstract N2 - 158 Objectives There is currently no PET radioligand available for direct imaging of the D3 receptor, however the D2/D3 agonist [11C]-(+)-PHNO has been shown to exhibit preferential affinity for D3. The work presented here explores and validates the utility of [11C]-(+)-PHNO to image D3 receptors in humans by using a highly selective D3 antagonist to dissect the regional [11C]-(+)-PHNO signal into D3 and D2 components. Methods [11C]-(+)-PHNO PET studies were performed in 19 healthy human volunteers. Each subject received dynamic PET scans at baseline and following one or more oral doses of the highly selective D3 antagonist GSK598809. The simplified reference tissue model was applied on both an ROI and voxelwise basis. The resulting binding potential data were fitted to a one site competition model describing the binding of GSK598809 to D3 and D2, producing both regional and parametric estimates of the fractions of baseline [11C]-(+)-PHNO signal corresponding to D3. Results Estimates of the regional D3 fractions of [11C]-(+)-PHNO BPND were: substantia nigra: 100% ± 21%, globus pallidus: 67% ± 13%, ventral striatum: 26% ± 9%, thalamus: 46% ± 54% dorsal caudate: 1% ± 13%, dorsal putamen: 0% ± 11%. Parametric images of D3 fractions were consistent with the regional analysis. A small dose-dependent decrease in the [11C]-(+)-PHNO signal in the cerebellum was observed but the effect of this on occupancy calculations was assessed to be small. Conclusions These results further elucidate the distribution of D3 and D2 receptors in the living human brain. The near-complete blockade of [11C]-(+)-PHNO binding achieved in the substantia nigra supports its use for imaging of D3 occupancy in drug development ER -