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

Abstract

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