title: Rostrocaudal gradients of dopamine D2/3 receptor binding in striatal subregions measured with [(11)C]raclopride and high-resolution positron emission tomography.
abstract: The human striatum has structural and functional subdivisions, both dorsoventrally and rostrocaudally. To date, the gradients of dopamine D2/3 receptor binding in the human striatum have not been measured with positron emission tomography (PET). Seven healthy male subjects aged 24.5 ± 3.5 years were scanned with brain-dedicated high-resolution research tomography (HRRT, Siemens Medical Solutions, Knoxville, TN, USA) and [(11)C]raclopride. Coronally defined regions of interest (ROIs) of the caudate nucleus, putamen and ventral striatum (VST) were sampled plane-by-plane, 1.5mm apart, on spatially normalized binding potential (BPND) images. Regional [(11)C]raclopride BPND values were calculated using the simplified reference tissue model (SRTM) from a total of 25 coronal planes. An increasing rostrocaudal gradient of the D2/3 receptor binding was detected in the putamen, which is consistent with the known distribution of D2/3 dopamine receptors. In the caudate nucleus, there was an initial increase in the BPND values in the most anterior planes, suggesting that the highest D2/3 receptor binding occurred in the head; however, there was an overall descending gradient. A declining trend was also observed in the VST. The novelty of this study lies in the presentation, for the first time, of the D2/3 receptor binding gradients in each striatal subregion in the brains of living healthy humans. The high spatial resolution provided by HRRT enables frequent sampling of BPND along the longitudinal extent of striatum; this method is superior to the sectioning used in previous post mortem studies. Regarding the functional organization of the striatum, our findings can inform future investigations of normal neurophysiology as well as efforts to differentiate neuropsychiatric disorders affecting the brain dopamine (DA) system. Furthermore, the average distribution of D2/3 receptor binding revealed in this study could serve as a basis for a database that includes distributions of various DA markers as a function of healthy aging.
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, PO Box 52, FIN-20521 Turku, Finland. khalak@utu.fi
authors.forename: Kati
authors.initials: K
authors.lastname: Alakurtti
authors.forename: Jarkko J
authors.initials: JJ
authors.lastname: Johansson
authors.forename: Terhi
authors.initials: T
authors.lastname: Tuokkola
authors.forename: Kjell
authors.initials: K
authors.lastname: Någren
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
mesh_terms: D001921:Brain / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D020891:Raclopride; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D020891:Raclopride
keywords: AC; AP; BP(ND); D(2/3) receptors; DA; DAT; DCA; DPU; Dopamine; Gradient; HRRT; MSA; PET; PSP; PVE; ROI; SRTM; TAC; VST; Ventral striatum; [(11)C]raclopride; anterior commissure; anterior–posterior; dopamine; dopamine transporter; dorsal caudate nucleus; dorsal putamen; high-resolution research tomography; multiple system atrophy; non-displaceable binding potential; partial volume effect; positron emission tomography; progressive supranuclear palsy; region of interest; simplified reference tissue model; time–activity curve; ventral striatum