title: A comparative evaluation of the dopamine D(2/3) agonist radiotracer [11C](-)-N-propyl-norapomorphine and antagonist [11C]raclopride to measure amphetamine-induced dopamine release in the human striatum.
abstract: (-)-N-Propyl-norapomorphine (NPA) is a full dopamine D(2/3) receptor agonist, and [(11)C]NPA is a suitable radiotracer to image D(2/3) receptors configured in a state of high affinity for agonists with positron emission tomography (PET). In this study, the vulnerability of the in vivo binding of [11C]NPA to acute fluctuation in synaptic dopamine was assessed with PET in healthy humans and compared with that of the reference D(2/3) receptor antagonist radiotracer [11C]raclopride. Ten subjects (eight females and two males) were studied on two separate days, a minimum of 1 week apart, both with [11C]raclopride and [11C]NPA at baseline and after the administration of 0.5 mg x kg(-1) oral d-amphetamine. Kinetic modeling with an arterial input function was used to derive the binding potential relative to nonspecific uptake (BPND) in the ventral striatum (VST), caudate (CAD), and putamen (PUT). [11C]Raclopride BPND was significantly reduced by 9.7 +/- 4.4, 8.4 +/- 4.2, and 14.7 +/- 4.8% after amphetamine administration in the VST, CAD, and PUT. [11C]NPA BPND was also reduced significantly, by 16.0 +/- 7.0, 16.1 +/- 6.1, and 21.9 +/- 4.9% after the same dose of amphetamine in the VST, CAD, and PUT. Although these results suggest that [11C]NPA is more vulnerable to endogenous competition by dopamine compared with [11C]raclopride by a factor of 1.49 to 1.90, the same data for a related outcome measure, binding potential relative to plasma concentration, was not significant. Nevertheless, these data add to the growing literature that suggests D(2/3) agonist radiotracers are more vulnerable to endogenous competition by dopamine than existing D(2/3) antagonist radiotracers.
authors.affiliation: Department of Radiology, University of Pittsburgh Medical Center Presbyterian, PET Facility, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. narendranr@upmc.edu
authors.forename: Rajesh
authors.initials: R
authors.lastname: Narendran
authors.forename: N Scott
authors.initials: NS
authors.lastname: Mason
authors.forename: Charles M
authors.initials: CM
authors.lastname: Laymon
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lopresti
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Velasquez
authors.forename: Maureen A
authors.initials: MA
authors.lastname: May
authors.forename: Steve
authors.initials: S
authors.lastname: Kendro
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: W Gordon
authors.initials: WG
authors.lastname: Frankle
mesh_terms: D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D020891:Raclopride; C009074:N-n-propylnorapomorphine; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine