Positron emission tomography quantification of [11C]-(+)-PHNO binding to the dopamine D2/D3 receptors in the human brain

In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

“…A study conducted to characterize the in vivo pharmacokinetics and pharmacological properties of [ 11 C]PHNO at the D3 receptor in rats used an intracerebral beta-sensitive system [45]. Shortly thereafter, PET studies using [ 11 C]PHNO were reported in cats and humans [60,61]. The present study suggests that it is a typical phenomenon in rats that D3 receptor ligands belonging to the carboxamide type are taken up into the ventricular system, simultaneously showing high specific binding in the pituitary gland.…”

Synthesis and Characterization of a Novel Series of Agonist Compounds as Potential Radiopharmaceuticals for Imaging Dopamine D2/3 Receptors in Their High-Affinity State

“…These compounds are of different chemical classes, including ergolines, aporphines, 2-aminotetralins, benzoquinolines, and naphthoxazines. Aporphines [ 11 C]NPA ( N -propylnorapomorphine) and [ 11 C]MNPA (2-methoxy- N -propylnorapomorphine) and naphthoxazine [ 11 C]PHNO (4-propyl-9-hydroxynaphthoxazine) turned out to be the most successful agonists and have also been evaluated as PET tracers in man. , In humans, agonists [ 11 C]PHNO and [ 11 C]NPA showed better sensitivity for the detection of endogenous dopamine release than antagonist [ 11 C]raclopride. − All three of these tracers also performed better than [ 11 C]raclopride in dopamine-release measurement in rodents, pigs, cats, and nonhuman primates . This corroborates the notion that agonist radiotracers are more prone to detect changes in neurotransmitter concentrations than antagonist tracers.…”

“…This corroborates the notion that agonist radiotracers are more prone to detect changes in neurotransmitter concentrations than antagonist tracers. However, all D 2/3 agonist PET ligands successfully evaluated in humans are [ 11 C]-labeled. , Because of the short half-life (20.4 min) of carbon-11, these radioligands can be used only when a cyclotron is present on-site. This expensive device is, however, available in only a minority of hospitals.…”