Small effect of dopamine release and no effect of dopamine depletion on [18F]fallypride binding in healthy humans.
Molecular imaging has been used to estimate both drug-induced and tonic dopamine release in the striatum and most recently extrastriatal areas of healthy humans. However, to date, studies of drug-induced and tonic dopamine release have not been performed in the same subjects. This study performed positron emission tomography (PET) with [18F]fallypride in healthy subjects to assess (1) the reproducibility of [18F]fallypride and (2) both D-amphetamine-induced and alpha-methyl-p-tyrosine (AMPT)-induced changes in dopamin release on [(18)F]fallypride binding in striatal and extrastriatal areas. Subjects underwent [18F]fallypride PET studies at baseline and following oral D-amphetamine administration (0.5 mg/kg) and oral AMPT administration (3 g/70 kg/day over 44 h). Binding potential (BP) (BP(ND)) of [18F]fallypride was calculated in striatal and extrastriatal areas using a reference region method. Percent change in regional BP(ND) was computed and correlated with change in cognition and mood. Test-retest variability of [18F]fallypride was low in both striatal and extrastriatal regions. D-Amphetamine significantly decreased BP(ND) by 8-14% in striatal subdivisions, caudate, putamen, substantia nigra, medial orbitofrontal cortex, and medial temporal cortex. Correlation between change in BP(ND) and verbal fluency was seen in the thalamus and substantia nigra. In contrast, depletion of endogenous dopamine with AMPT did not effect [18F]fallypride BP(ND) in both striatum and extrastriatal regions. These findings indicate that [18F]fallypride is useful for measuring amphetamine-induced dopamine release, but may be unreliable for estimating tonic dopamine levels, in striatum and extrastriatal regions of healthy humans.
Cropley
Vanessa L
VL
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-0135, USA.
Innis
Robert B
RB
Nathan
Pradeep J
PJ
Brown
Amira K
AK
Sangare
Janet L
JL
Lerner
Alicja
A
Ryu
Yong Hoon
YH
Sprague
Kelly E
KE
Pike
Victor W
VW
Fujita
Masahiro
M
D000284:Administration, Oral; D000328:Adult; D000661:Amphetamine / Q000008:administration & dosage; D000704:Analysis of Variance; D001549:Benzamides / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D011759:Pyrrolidines / Q000378:metabolism*; D015203:Reproducibility of Results; D019805:alpha-Methyltyrosine / Q000008:administration & dosage
D001549:Benzamides; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D019805:alpha-Methyltyrosine; D000661:Amphetamine; D004298:Dopamine