title: Molecular imaging of brain localization of liposomes in mice using MALDI mass spectrometry.
abstract: Phospholipids have excellent biocompatibility and are therefore often used as main components of liposomal drug carriers. In traditional bioanalytics, the in-vivo distribution of liposomal drug carriers is assessed using radiolabeled liposomal constituents. This study presents matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) as an alternative, label-free method for ex-vivo molecular imaging of liposomal drug carriers in mouse tissue. To this end, indocyanine green as cargo and two liposomal markers, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with monodisperse polyethylene glycol (PEG36-DSPE) were incorporated into liposomal carriers and administered to mice. We used MALDI MSI of the two lipid markers in both positive and negative ion mode for visualization of liposome integrity and distribution in mouse organs. Additional MSI of hemoglobin in the same tissue slice and pixel-by-pixel computational analysis of co-occurrence of lipid markers and hemoglobin served as indicator of liposome localization either in parenchyma or in blood vessels. Our proof-of-concept study suggests that liposomal components and indocyanine green distributed into all investigated organs.
authors.affiliation: Center for Applied Research in Applied Biomedical Mass Spectrometry (ABIMAS). Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.|Instrumental Analytics and Bioanalytics, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Fülöp
authors.affiliation: Center for Applied Research in Applied Biomedical Mass Spectrometry (ABIMAS). Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.|Instrumental Analytics and Bioanalytics, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Sammour
authors.affiliation: Center for Applied Research in Applied Biomedical Mass Spectrometry (ABIMAS). Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.|Instrumental Analytics and Bioanalytics, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Erich
authors.affiliation: Lipid Pathobiochemistry, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: von Gerichten
authors.affiliation: Phospholipid Research Center, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: van Hoogevest
authors.affiliation: Center for Applied Research in Applied Biomedical Mass Spectrometry (ABIMAS). Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.|Lipid Pathobiochemistry, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Roger
authors.initials: R
authors.lastname: Sandhoff
authors.affiliation: Center for Applied Research in Applied Biomedical Mass Spectrometry (ABIMAS). Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.|Instrumental Analytics and Bioanalytics, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.|Institute of Medical Technology, University of Heidelberg and Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Hopf
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D007208:Indocyanine Green / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008081:Liposomes; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D008081:Liposomes; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D011092:Polyethylene Glycols; D007208:Indocyanine Green; C030345:1,2-dipalmitoylphosphatidylglycerol