A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

F-18-labeling syntheses and preclinical evaluation of functionalized nanoliposomes for Alzheimer's disease




TekijätRokka J, Snellman A, Kaasalainen M, Salonen J, Zona C, La Ferla B, Nicotra F, Re F, Masserini M, Forsback S, Lopez-Picon F, Rinne JO, Haaparanta-Solin M, Solin O

KustantajaELSEVIER SCIENCE BV

Julkaisuvuosi2016

JournalEuropean Journal of Pharmaceutical Sciences

Tietokannassa oleva lehden nimiEUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Lehden akronyymiEUR J PHARM SCI

Vuosikerta88

Aloitussivu257

Lopetussivu266

Sivujen määrä10

ISSN0928-0987

eISSN1879-0720

DOIhttps://doi.org/10.1016/j.ejps.2016.03.016


Tiivistelmä
The aim of the present study was to synthesize functionalized F-18-labeled NLs (F-18-NLs) and evaluate their biological behavior in mouse models of Alzheimer's disease (AD) using positron emission tomography (PET) and ex vivo brain autoradiography. F-18-fluorine was introduced to 18F-NLs either by using a core forming F-18-lipid or by encapsulating a F-18-tracer, F-18-treg-curcumin inside the NLs. Phosphatidic acid (PA) and curcumin derivative (Curc) functionalized F-18-NLs with or without additional mApoE functionalization were produced using thin film hydration. The biodistribution and beta-amyloid plaque-binding ability of F-18-NLs were studied in wild type mice and AD mouse models using in vivo PET imaging and ex vivo brain autoradiography at 60 min after F-18-NL injection.Functionalized F-18-NLs were successfully synthesized. The preclinical evaluation in mice showed that the functional group affected the biodistribution of F-18-NLs. Further functionalization with mApoE increased the brain-to-blood ratio of F-18-NLs but the overall brain uptake remained low with all functionalized F-18-NLs. The liposomal encapsulation of F-18-treg-curcumin was not successful and preclinical results of encapsulated F-18-treg-curcumin and plain F-18-treg-curcumin were identical.Although the studied functionalized F-18-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 F-18-labeled NLs. (C) 2016 Elsevier B.V. All rights reserved.



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