Visualizing hepatic copper release in Long-Evans cinnamon rats using single-photon emission computed tomography

Eric M. Yezdimer, Tomohiro Umemoto, Hiroshi Yamada, Satoshi Makino, Ikuo Tooyama

研究成果: Article査読

1 被引用数 (Scopus)

抄録

The potential utility of an imaging agent for the detection of hepatic copper was investigated in a Wilson's disease animal model. Solid-phase peptide synthesis was used to construct an imaging agent which consisted of a copper-binding moiety, taken from the prion protein, and a gamma ray-emitting indium radiolabel. Long-Evans Cinnamon (LEC) rats were used for the Wilson's disease animal model. Our evaluation methodology consisted of administering the indium-labeled agent to both LEC and genetically healthy Long-Evans (LE) cohorts via a tail vein injection and following the pharmacokinetics with single-photon emission computed tomography (SPECT) over the course of an hour. The animals were then sacrificed and their livers necropsied. An additional control agent, lacking the copper-binding moiety, was used to gauge whether any change in the hepatic uptake might be caused by other physiological differences between the two animal models. LEC rats injected with the indium-labeled agent had roughly double the amount of hepatic radioactivity as compared to the healthy control animals. The control agent, without the copper-binding moiety, displayed a hepatic signal similar to that of the control LE animals. Additional intraperitoneal spiking with CuSO4 in C57BL/6 mice also found that the pharmacokinetics of the indium-labeled, prion-based imaging agent is profoundly altered by exposure to in vivo pools of extracellular copper. The described SPECT application with this compound represented a significant improvement over a previous MRI application using the same base peptide sequence.

本文言語English
ページ(範囲)1138-1150
ページ数13
ジャーナルApplied Biochemistry and Biotechnology
170
5
DOI
出版ステータスPublished - 2013 7
外部発表はい

ASJC Scopus subject areas

  • バイオテクノロジー
  • バイオエンジニアリング
  • 生化学
  • 応用微生物学とバイオテクノロジー
  • 分子生物学

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