title: No effect of dopamine depletion on the binding of the high-affinity D 2/3 radiotracer [11C]FLB 457 in the human cortex.
abstract: The use of PET and SPECT endogenous competition-binding techniques has contributed to the understanding of the role of dopamine (DA) in several neuropsychiatric disorders. An important limitation of these imaging studies is the fact that measurements of changes in synaptic DA have been restricted to the striatum. The ligands previously used, such as [(11)C]raclopride and [(123)I]IBZM, do not provide sufficient signal-to-noise ratio to quantify D(2) receptors in extrastriatal areas, such as cortex, where the concentration of D(2) receptors is much lower than that in the striatum. Recently, we published a comparison study of the ability of two high-affinity DA D(2) radioligands [(11)C]FLB 457 and [(11)C]fallypride to measure amphetamine-induced changes in DA transmission in the human cortex. Our findings support the use of [(11)C]FLB 457 to measure changes in cortical synaptic DA induced by amphetamine. The goal of this study is to examine the effects of DA depletion with α-methyl-para-tyrosine (α-MPT) on [(11)C]FLB 457 binding in the cortex. Six healthy volunteers underwent two PET scans, first under control conditions and subsequently after DA depletion. The simplified reference tissue model as well as kinetic modeling with an arterial input function was used to derive the binding potential (BP(ND)) in seven cortical regions. We found no effect of DA depletion with α-MPT on [(11)C]FLB 457 binding in any of the regions examined. In contrast to the measurement of DA release, the combination of low D(2) receptor density and low basal DA levels in the cortex greatly reduce the power to detect alterations in [(11)C]FLB 457 binding secondary to DA depletion.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. franklewg@upmc.edu
authors.forename: W Gordon
authors.initials: WG
authors.lastname: Frankle
authors.forename: N Scott
authors.initials: NS
authors.lastname: Mason
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.forename: Khanum
authors.initials: K
authors.lastname: Ridler
authors.forename: Maureen A
authors.initials: MA
authors.lastname: May
authors.forename: Deanna
authors.initials: D
authors.lastname: Asmonga
authors.forename: Chi-Min
authors.initials: CM
authors.lastname: Chen
authors.forename: Steve
authors.initials: S
authors.lastname: Kendro
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cooper
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: Rajesh
authors.initials: R
authors.lastname: Narendran
mesh_terms: D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency* / Q000502:physiology; D018492:Dopamine Antagonists / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D011759:Pyrrolidines / Q000378:metabolism*; D011877:Radionuclide Imaging; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D055815:Young Adult; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D002250:Carbon Radioisotopes; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; C065065:FLB 457; D019805:alpha-Methyltyrosine; D004298:Dopamine