Synthesis and evaluation of a 18F-curcumin derivate for β-amyloid plaque imaging

Introduction: Curcumin is a neuroprotective compound that inhibits the formation of amyloid oligomers and fibrils and binds to beta-amyloid plaques in Alzheimer's disease (AD). We aimed to synthesize an F-18-labeled curcumin derivate ([F-18]4) and to characterize its positron emission tomography (PET) tracer-binding properties to beta-amyloid plaques in a transgenic APP23 mouse model of AD. Methods: We utilized facile one-pot synthesis of [F-18]4 using nucleophilic F-18-fluorination and click chemistry. Binding of [F-18]4 to beta-amyloid plaques in the transgenic APP23 mouse brain cryosections was studied in vitro using heterologous competitive binding against PIB. [F-18]4 uptake was studied ex vivo in rodents and in vivo using PET/computed tomography of transgenic APP23 and wild-type control mice. Results: The radiochemical yield of [F-18]4 was 21 +/- 11%, the specific activity exceeded 1 TBq/mu mol, and the radiochemical purity exceeded 99.3% at the end of synthesis. In vitro studies of [F-18]4 with the transgenic APP23 mouse revealed high beta-amyloid plaque binding. In vivo and ex vivo studies demonstrated that [F-18]4 has fast clearance from the blood, moderate metabolism but low blood-brain barrier (BBB) penetration. Conclusions: [F-18]4 was synthesized in high yield and excellent quality. In vitro studies, metabolite profile, and fast clearance from the blood indicated a promising tracer for A beta imaging. However, [F-18]4 has low in vivo BBB penetration and thus further studies are needed to reveal the reason for this and to possibly overcome this issue. (C) 2014 Elsevier Ltd. All rights reserved.