title: Multiphoton microscopy and fluorescence lifetime imaging provide a novel method in studying drug distribution and metabolism in the rat liver in vivo.
abstract: Multiphoton microscopy has been shown to be a useful tool in studying drug distribution in biological tissues. In addition, fluorescence lifetime imaging provides information about the structure and dynamics of fluorophores based on their fluorescence lifetimes. Fluorescein, a commonly used fluorescent probe, is metabolized within liver cells to fluorescein mono-glucuronide, which is also fluorescent. Fluorescein and its glucuronide have similar excitation and emission spectra, but different fluorescence lifetimes. In this study, we employed multiphoton fluorescence lifetime imaging to study the distribution and metabolism of fluorescein and its metabolite in vivo in rat liver. Fluorescence lifetime values in vitro were used to interpret in vivo data. Our results show that the mean fluorescence lifetimes of fluorescein and its metabolite decrease over time after injection of fluorescein in three different regions of the liver. In conclusion, we have demonstrated a novel method to study a fluorescent compound and metabolite in vivo using multiphoton fluorescence lifetime imaging.
authors: University of Queensland, School of Medicine, Woolloongabba, Queensland, 4102, Australia.
authors: Camilla A
authors: CA
authors: Thorling
authors: Yuri
authors: Y
authors: Dancik
authors: Clinton W
authors: CW
authors: Hupple
authors: Gregory
authors: G
authors: Medley
authors: Xin
authors: X
authors: Liu
authors: Andrei V
authors: AV
authors: Zvyagin
authors: Tom A
authors: TA
authors: Robertson
authors: Frank J
authors: FJ
authors: Burczynski
authors: Michael S
authors: MS
authors: Roberts
mesh_terms: D061354:Acinar Cells; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D005452:Fluoresceins / Q000032:analysis / Q000493:pharmacokinetics*; D006651:Histocytochemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D008956:Models, Chemical; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D005452:Fluoresceins; C041357:fluorescein glucuronide