title: Analysis of Extrastriatal123I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases.
abstract: 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT can visualize and quantify striatal dopamine transporter (DAT) binding in vivo. In addition,123I-FP-CIT has modest affinity for the serotonin transporter (SERT), predominantly represented in extrastriatal binding. On the basis of previous imaging studies that have suggested more pronounced degeneration of other monoaminergic systems in multiple-system atrophy (MSA) and progressive supranuclear palsy (PSP) than in Parkinson disease (PD), we hypothesized that, in addition to striatal DAT binding, there would be differences in extrastriatal123I-FP-CIT SPECT binding to SERT between MSA, PSP, and PD.Methods:We included patients with parkinsonian type MSA (multiple-system atrophy with predominantly parkinsonism [MSA-P],n= 9), cerebellar type MSA (MSA-C,n= 7), PSP (n= 13), and PD (n= 30).123I-FP-CIT binding was analyzed using region-of-interest (ROI)- as well as voxel-based methods in both the DAT-rich striatum (caudate nucleus and putamen) and the SERT-rich extrastriatal brain regions (thalamus, hypothalamus, and pons). For SERT analysis, patients on selective serotonin reuptake inhibitor were excluded (n= 48 remained).Results:In the ROI analyses, extrastriatal123I-FP-CIT binding ratios in the hypothalamus were significantly lower in PSP than in MSA-C patients, and we observed significantly lower striatal123I-FP-CIT binding ratios in the caudate nucleus of PSP patients than in that of both PD and MSA-C patients. In the posterior putamen, binding ratios were significantly lower in MSA-P, PSP, and PD than MSA-C patients. Striatal ROI outcomes were confirmed by the voxel-based analyses that additionally showed a significantly lower hypothalamic binding in PSP and MSA-P than PD.Conclusion:Striatal123I-FP-CIT binding to DAT and hypothalamic123I-FP-CIT binding to SERT are significantly lower in MSA-P and PSP than in PD and MSA-C patients and might therefore be of interest for differential diagnosis.
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands me.joling@vumc.nl.|Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands.|Amsterdam Neuroscience, Amsterdam, The Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Merijn
authors.initials: M
authors.lastname: Joling
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.|Amsterdam Neuroscience, Amsterdam, The Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Vriend
authors.affiliation: Amsterdam Neuroscience, Amsterdam, The Netherlands.|Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Odile A
authors.initials: OA
authors.lastname: van den Heuvel
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; and.
authors.forename: Pieter G H M
authors.initials: PGHM
authors.lastname: Raijmakers
authors.affiliation: GE Healthcare, The Grove Centre, Amersham, United Kingdom.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Jones
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.|Amsterdam Neuroscience, Amsterdam, The Netherlands.
authors.forename: Henk W
authors.initials: HW
authors.lastname: Berendse
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands.|Amsterdam Neuroscience, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D003937:Diagnosis, Differential; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000493:pharmacokinetics*
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
keywords: 123I-FP-CIT SPECT; DAT; Parkinson’s disease; SERT; multiple system atrophy; progressive supranuclear palsy