title: Striatal and extrastriatal dopamine release measured with PET and [(18)F] fallypride.
abstract: The amphetamine challenge, in which positron emission tomography (PET) or single photon emission computed tomography radioligand binding following administration of amphetamine is compared to baseline values, has been successfully used in a number of brain imaging studies as an indicator of dopaminergic function, particularly in the striatum. [(18)F] fallypride is the first PET radioligand that allows measurement of the effects of amphetamine on D2/D3 ligand binding in striatum and extra-striatal brain regions in a single scanning session following amphetamine. We scanned 15 healthy volunteer subjects with [(18)F] fallypride at baseline and following amphetamine (0.3 mg/kg) using arterial plasma input-based modeling as well as reference region methods. We found that amphetamine effect was robustly detected in ventral striatum, globus pallidus, and posterior putamen, and with slightly higher variability in other striatal subregions. However, the observed effect sizes in striatum were less than those observed in previous studies in our laboratory using [(11)C] raclopride. Robust effect was also detected in limbic extra-striatal regions (hippocampus, amygdala) and substantia nigra, but the signal-to-noise ratio was too low to allow accurate measurement in cortical regions. We conclude that [(18)F] fallypride is a suitable ligand for measuring amphetamine effect in striatum and limbic regions, but it is not suitable for measuring the effect in cortical regions and may not provide the most powerful way to measure the effect in striatum.
authors.affiliation: Columbia University, New York, NY, USA. mms218@columbia.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.forename: Judy L
authors.initials: JL
authors.lastname: Thompson
authors.forename: Nina
authors.initials: N
authors.lastname: Urban
authors.forename: John
authors.initials: J
authors.lastname: Castrillon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hackett
authors.forename: S-A
authors.initials: SA
authors.lastname: Bae
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
mesh_terms: D000328:Adult; D000661:Amphetamine / Q000494:pharmacology; D001549:Benzamides; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011759:Pyrrolidines; D020891:Raclopride; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
chemical_list: D001549:Benzamides; D015259:Dopamine Agents; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine