Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and Evaluation of Oleanolic Acid-Conjugated Lactoferrin for β-Amyloid Plaque Imaging

  • Kim, Sung-Min (Division of Magnetic Resonance Research, Korea Basic Science Institute) ;
  • Kim, Dongkyu (Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF)) ;
  • Chae, Min Kyung (Division of Magnetic Resonance Research, Korea Basic Science Institute) ;
  • Jeong, Il-Ha (Division of Magnetic Resonance Research, Korea Basic Science Institute) ;
  • Cho, Jee-Hyun (Division of Magnetic Resonance Research, Korea Basic Science Institute) ;
  • Choi, Naeun (Division of Magnetic Resonance Research, Korea Basic Science Institute) ;
  • Lee, Kyo Chul (Molecular Imaging Research Center, Research Institute of Radiological & Medical Science, Korea Institute of Radiological & Medical Science (KIRAMS)) ;
  • Lee, Chulhyun (Division of Magnetic Resonance Research, Korea Basic Science Institute) ;
  • Ryu, Eun Kyoung (Division of Magnetic Resonance Research, Korea Basic Science Institute)
  • Received : 2012.06.30
  • Accepted : 2012.08.13
  • Published : 2012.11.20
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Abstract

${\beta}$-Amyloid accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD). Since early detection of ${\beta}$-amyloid may facilitate more successful and timely therapeutic interventions, many investigators have focused on developing AD diagnostic reagents that can penetrate the blood-brain barrier (BBB). Oleanolic acid (OA) is a substance found in a variety of plants that has been reported to prevent the progression of AD in mice. In this study, we synthesized and evaluated a new radioligand in which OA was conjugated to lactoferrin (Lf, an iron-binding glycoprotein that crosses the BBB) for the diagnosis of AD. In an in vitro study in which OA-Lf was incubated with ${\beta}$-amyloid (1-42) aggregates for 24 h, we found that OA-Lf effectively inhibited ${\beta}$-amyloid aggregation and fibril formation. In vivo studies demonstrated that $^{123}I$-OA-Lf brain uptake was higher than$^{123}I$-Lf uptake. Therefore, radiolabeled OA-Lf may have diagnostic potential for ${\beta}$-amyloid imaging.

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References

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