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

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• 作者：Johanna Rokka^a ; ^{johanna.rokka@utu.fi" class="auth_mail" title="E-mail the corresponding author} ; Anniina Snellman^b ; ^c ; Martti Kaasalainen^d ; Jarno Salonen^d ; Cristiano Zona^e ; Barbara La Ferla^e ; Francesco Nicotra^e ; Francesca Re^f ; Massimo Masserini^f ; Sarita Forsback^a ; Francisco Lopez-Picon^b ; ^c ; Juha O. Rinne^g ; ^h ; Merja Haaparanta-Solin^b ; ^c ; Olof Solin^a ; ⁱ ; ^j
• 关键词：Positron emission tomography (PET) ; Nucleophilic 18F-fluorination ; Functionalized nanoliposomes ; Alzheimer's disease ; β-amyloid plaques
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：10 June 2016
• 年：2016
• 卷：88
• 期：Complete
• 页码：257-266
• 全文大小：1881 K

文摘

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 60 min 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.