title: In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography.
abstract: Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [(18)F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [(11)C]-PIB (Pittsburg compound B) have shown exceptional value in animal models and AD patients. Previously, the glucose analogue [(18)F]-FDG (2-[(18)F]fluorodeoxyglucose) allowed researchers and clinicians to evaluate the brain glucose consumption and proved its utility for the early diagnosis and the monitoring of the progression of AD. Animal models of AD are based on the transgenic expression of different human mutant genes linked to familial AD. The novel transgenic 5XFAD mouse containing 5 mutated genes in its genome has been proposed as an AD model with rapid and massive cerebral amyloid deposition. PET studies performed with animal-dedicated scanners indicate that PET with amyloid-targeted radiotracers can detect the pathological amyloid deposition in transgenic mice and rats. However, in other studies no differences were found between transgenic mice and their wild type littermates. We sought to investigate in 5XFAD mice if the radiotracers [(11)C]-PIB, and [(18)F]-Florbetapir could quantify the amyloid deposition in vivo and if [(18)F]-FDG could do so with regard to glucose consumption. We found that 5XFAD animals presented higher cerebral binding of [(18)F]-Florbetapir, [(11)C]-PIB, and [(18)F]-FDG. These results support the use of amyloid PET radiotracers for the evaluation of AD animal models. Probably, the increased uptake observed with [(18)F]-FDG is a consequence of glial activation that occurs in 5XFAD mice.
authors: CRC Centre d'Imatge Molecular, CRC Corporació Sanitària, Barcelona, Spain. srojas@crccorp.es
authors: Santiago
authors: S
authors: Rojas
authors: José Raúl
authors: JR
authors: Herance
authors: Juan Domingo
authors: JD
authors: Gispert
authors: Sergio
authors: S
authors: Abad
authors: Elia
authors: E
authors: Torrent
authors: Xavier
authors: X
authors: Jiménez
authors: Deborah
authors: D
authors: Pareto
authors: Unai
authors: U
authors: Perpiña
authors: Sara
authors: S
authors: Sarroca
authors: Elisenda
authors: E
authors: Rodríguez
authors: Arantxa
authors: A
authors: Ortega-Aznar
authors: Coral
authors: C
authors: Sanfeliu
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles / Q000378:metabolism
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D005947:Glucose