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

: Rokka 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

Publisher: ELSEVIER SCIENCE BV

: 2016

: European Journal of Pharmaceutical Sciences

: EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

: EUR J PHARM SCI

: 88

: 257

: 266

: 10

: 0928-0987

: 1879-0720

DOI: https://doi.org/10.1016/j.ejps.2016.03.016

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.