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Revisiting the Radiosynthesis of [(18)F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer’s Disease

[(18)F]FPEB is a positron emission tomography (PET) radiopharmaceutical used for imaging the abundance and distribution of mGluR5 in the central nervous system (CNS). Efficient radiolabeling of the aromatic ring of [(18)F]FPEB has been an ongoing challenge. Herein, five metal-free precursors for the...

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Detalles Bibliográficos
Autores principales: Varlow, Cassis, Murrell, Emily, Holland, Jason P., Kassenbrock, Alina, Shannon, Whitney, Liang, Steven H., Vasdev, Neil, Stephenson, Nickeisha A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070414/
https://www.ncbi.nlm.nih.gov/pubmed/32098347
http://dx.doi.org/10.3390/molecules25040982
Descripción
Sumario:[(18)F]FPEB is a positron emission tomography (PET) radiopharmaceutical used for imaging the abundance and distribution of mGluR5 in the central nervous system (CNS). Efficient radiolabeling of the aromatic ring of [(18)F]FPEB has been an ongoing challenge. Herein, five metal-free precursors for the radiofluorination of [(18)F]FPEB were compared, namely, a chloro-, nitro-, sulfonium salt, and two spirocyclic iodonium ylide (SCIDY) precursors bearing a cyclopentyl (SPI5) and a new adamantyl (SPIAd) auxiliary. The chloro- and nitro-precursors resulted in a low radiochemical yield (<10% RCY), whereas both SCIDY precursors and the sulfonium salt precursor produced [(18)F]FPEB in the highest RCYs of 25% and 36%, respectively. Preliminary PET/CT imaging studies with [(18)F]FPEB were conducted in a transgenic model of Alzheimer’s Disease (AD) using B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) mice, and data were compared with age-matched wild-type (WT) B6C3F1/J control mice. In APP/PS1 mice, whole brain distribution at 5 min post-injection showed a slightly higher uptake (SUV = 4.8 ± 0.4) than in age-matched controls (SUV = 4.0 ± 0.2). Further studies to explore mGluR5 as an early biomarker for AD are underway.