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001-es BibID:BIBFORM080177
035-os BibID:(PMID)31307287
Első szerző:Bertoglio, Daniele
Cím:Validation and noninvasive kinetic modeling of [11C]UCB-J PET imaging in mice / Daniele Bertoglio, Jeroen Verhaeghe, Alan Miranda, Istvan Kertesz, Klaudia Cybulska, Špela Korat, Leonie Wyffels, Sigrid Stroobants, Ladislav Mrzljak, Celia Dominguez, Longbin Liu, Mette Skinbjerg, Ignacio Munoz-Sanjuan, Steven Staelens
Dátum:2020
Megjegyzések:Synaptic pathology is associated with several brain disorders, thus positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) using the radioligand [11C]UCB-J may provide a tool to measure synaptic alterations. Given the pivotal role of mouse models in understanding neuropsychiatric and neurodegenerative disorders, this study aims to validate and characterize [11C]UCB-J in mice. We performed a blocking study to verify the specificity of the radiotracer to SV2A, examined kinetic models using an image-derived input function (IDIF) for quantification of the radiotracer, and investigated the in vivo metabolism. Regional TACs during baseline showed rapid uptake of [11C]UCB-J into the brain. Pretreatment with levetiracetam confirmed target engagement in a dose-dependent manner. VT (IDIF) values estimated with one- and two-tissue compartmental models (1TCM and 2TCM) were highly comparable (r=0.999, p<0.0001), with 1TCM performing better than 2TCM for K1 (IDIF). A scan duration of 60 min was sufficient for reliable VT (IDIF) and K1 (IDIF) estimations. In vivo metabolism of [11C]UCB-J was relatively rapid, with a parent fraction of 22.5±4.2% at 15 min p.i. In conclusion, our findings show that [11C]UCB-J selectively binds to SV2A with optimal kinetics in the mouse representing a promising tool to noninvasively quantify synaptic density in comparative or therapeutic studies in neuropsychiatric and neurodegenerative disorder models.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Journal of Cerebral Blood Flow and Metabolism. - 40 : 6 (2020), p. 1351-1362. -
További szerzők:Verhaeghe, Jeroen Miranda, Alan Kertész István (1966-) (vegyész) Cybulska, Klaudia Korat, Špela Wyffels, Leonie Stroobants, Sigrid Mrzljak, Ladislav Dominguez, Celia Liu, Longbin Skinbjerg, Mette Munoz-Sanjuan, Ignacio Staelens, Steven
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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