A radioiodinated nitroxide probe with improved stability against bioreduction for in vivo detection of lipid radicals

Risa Azuma, Toshihide Yamasaki, Kohei Sano, Masayuki Munekane, Yuta Matsuoka, Ken ichi Yamada, Takahiro Mukai

研究成果: Contribution to journalArticle査読

抄録

It is well known that lipid carbon radicals (lipid radicals) are the origin of lipid peroxidation and are involved in various diseases such as cancer. Therefore, the in vivo detection of lipid radicals would be expected to lead to early diagnosis of these diseases. However, there are no methods for measuring lipid radicals in vivo. Nitroxides are known to be highly reactive with lipid radicals, but they tend to be reduced in vivo. Focusing on the excellent detection sensitivity of nuclear medical imaging, we have developed a radioiodinated nitroxide derivative with resistance to bioreduction for the in vivo detection of lipid radicals. The desired compound was obtained successfully and was highly stable against bioreduction while maintaining high reactivity toward lipid radicals. The I-125 labeling was efficacious with radiochemical yields of 84–87% and radiochemical purities of >99%. A cellular uptake assay showed that the radioiodinated compound was significantly taken up by cells under lipid radical-producing conditions compared to that in the absence of lipid radical production. A biodistribution study indicated that the radioiodinated compound accumulated more in organs where lipid peroxidation was promoted than the methoxyamine derivative, which lost reactivity to lipid radicals. These results indicated that the developed probe became trapped in cells or organs by reacting with lipid radicals. Thus, the radioiodinated nitroxide is a candidate probe for in vivo detection of lipid radicals.

本文言語英語
ページ(範囲)297-305
ページ数9
ジャーナルFree Radical Biology and Medicine
163
DOI
出版ステータス出版済み - 2 1 2021

All Science Journal Classification (ASJC) codes

  • 生化学
  • 生理学(医学)

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