title: (18)F-labeling syntheses and preclinical evaluation of functionalized nanoliposomes for Alzheimer's disease.
abstract: The aim of the present study was to synthesize functionalized (18)F-labeled NLs ((18)F-NLs) and evaluate their biological behavior in mouse models of Alzheimer's disease (AD) using positron emission tomography (PET) and ex vivo brain autoradiography. (18)F-fluorine was introduced to (18)F-NLs either by using a core forming (18)F-lipid or by encapsulating a (18)F-tracer, (18)F-treg-curcumin inside the NLs. Phosphatidic acid (PA) and curcumin derivative (Curc) functionalized (18)F-NLs with or without additional mApoE functionalization were produced using thin film hydration. The biodistribution and β-amyloid plaque-binding ability of (18)F-NLs were studied in wild type mice and AD mouse models using in vivo PET imaging and ex vivo brain autoradiography at 60min after (18)F-NL injection. Functionalized (18)F-NLs were successfully synthesized. The preclinical evaluation in mice showed that the functional group affected the biodistribution of (18)F-NLs. Further functionalization with mApoE increased the brain-to-blood ratio of (18)F-NLs but the overall brain uptake remained low with all functionalized (18)F-NLs. The liposomal encapsulation of (18)F-treg-curcumin was not successful and preclinical results of encapsulated (18)F-treg-curcumin and plain (18)F-treg-curcumin were identical. Although the studied functionalized (18)F-NLs were not suitable for PET imaging as such, the synthesis techniques introduced in this study can be utilized to modify the biological behavior of (18)F-labeled NLs.
authors.affiliation: Turku PET Centre, Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku, Finland. Electronic address: johanna.rokka@utu.fi.
authors.forename: Johanna
authors.initials: J
authors.lastname: Rokka
authors.affiliation: Turku PET Centre, Preclinical Imaging, University of Turku, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Anniina
authors.initials: A
authors.lastname: Snellman
authors.affiliation: Laboratory of Industrial Physics, University of Turku, Finland.
authors.forename: Martti
authors.initials: M
authors.lastname: Kaasalainen
authors.affiliation: Laboratory of Industrial Physics, University of Turku, Finland.
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.affiliation: Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milano, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Zona
authors.affiliation: Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: La Ferla
authors.affiliation: Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicotra
authors.affiliation: Department of Health Science, University of Milano-Bicocca, Monza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Re
authors.affiliation: Department of Health Science, University of Milano-Bicocca, Monza, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Masserini
authors.affiliation: Turku PET Centre, Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku, Finland.
authors.forename: Sarita
authors.initials: S
authors.lastname: Forsback
authors.affiliation: Turku PET Centre, Preclinical Imaging, University of Turku, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopez-Picon
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.affiliation: Turku PET Centre, Preclinical Imaging, University of Turku, Turku, Finland; MediCity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Haaparanta-Solin
authors.affiliation: Turku PET Centre, Radiopharmaceutical Chemistry Laboratory, University of Turku, Turku, Finland; Turku PET Centre, Accelerator Laboratory, Åbo Akademi University, Turku, Finland; Department of Chemistry, University of Turku, Turku, Finland.
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000378:metabolism*; D005260:Female; D005461:Fluorine / Q000737:chemistry / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D041722:Genes, Transgenic, Suicide; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D013678:Technology, Pharmaceutical; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D008081:Liposomes; D019275:Radiopharmaceuticals; D005461:Fluorine
keywords: Alzheimer's disease; Functionalized nanoliposomes; Nucleophilic 18F-fluorination; Positron emission tomography (PET); β-amyloid plaques