title: Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.
abstract: With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195.
authors.affiliation: Chemical Works of Gedeon Richter Ltd., Gyomroi ut 19/21, H-1103 Budapest, Hungary. a.vas@richter.hu
authors.forename: Adám
authors.initials: A
authors.lastname: Vas
authors.forename: Yevgeni
authors.initials: Y
authors.lastname: Shchukin
authors.forename: Virginija D
authors.initials: VD
authors.lastname: Karrenbauer
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Cselényi
authors.forename: Kosta
authors.initials: K
authors.lastname: Kostulas
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.forename: Ivanka
authors.initials: I
authors.lastname: Savic
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D001667:Binding, Competitive; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005911:Gliosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000378:metabolism; D014748:Vinca Alkaloids / Q000737:chemistry
chemical_list: D000927:Anticonvulsants; D000970:Antineoplastic Agents; D015415:Biomarkers; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; D014748:Vinca Alkaloids; C013983:vinpocetine; C037850:PK 11195