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

Johanna Rokka, Anniina Snellman, Cristiano Zona, Barbara La Ferla, Francesco Nicotra, Mario Salmona, Gianluigi Forloni, Merja Haaparanta-Solin, Juha O. Rinne, Olof Solin

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction Curcumin is a neuroprotective compound that inhibits the formation of amyloid oligomers and fibrils and binds to β-amyloid plaques in Alzheimer's disease (AD). We aimed to synthesize an 18F-labeled curcumin derivate ([18F]4) and to characterize its positron emission tomography (PET) tracer-binding properties to β-amyloid plaques in a transgenic APP23 mouse model of AD. Methods We utilized facile one-pot synthesis of [18F]4 using nucleophilic 18F-fluorination and click chemistry. Binding of [18F]4 to β-amyloid plaques in the transgenic APP23 mouse brain cryosections was studied in vitro using heterologous competitive binding against PIB. [18F]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 [18F]4 was 21 ± 11%, the specific activity exceeded 1 TBq/μmol, and the radiochemical purity exceeded 99.3% at the end of synthesis. In vitro studies of [18F]4 with the transgenic APP23 mouse revealed high β-amyloid plaque binding. In vivo and ex vivo studies demonstrated that [18F]4 has fast clearance from the blood, moderate metabolism but low blood-brain barrier (BBB) penetration. Conclusions [ 18F]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 Aβ imaging. However, [18F]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.

Original languageEnglish
Pages (from-to)2753-2762
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number9
DOIs
Publication statusPublished - May 1 2014

Keywords

  • Alzheimer's disease
  • Click chemistry
  • Curcumin
  • Positron emission tomography (PET)
  • β-Amyloid

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

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