有機アニオントランスポーターOAT1と芳香族アミノ酸の相互作用を規定する分子内構造の同定： 腫瘍イメージングにおける腎臓バックグラウンド集積の低減に向けて

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  • 金 春烉
    大阪大・院医・生体システム薬理
  • 魏 玲
    大阪大・院医・生体システム薬理
  • 大垣 隆一
    大阪大・院医・生体システム薬理
  • 富永 英之
    福島県立医科大学ふくしま国際医療科学センター先端臨床研究センター
  • 奥田 傑
    大阪大・院医・生体システム薬理
  • 永森 收志
    大阪大・院医・生体システム薬理 奈良県立医科大・生体分子不均衡制御学
  • 金井 好克
    大阪大・院医・生体システム薬理

書誌事項

タイトル別名
  • Critical moieties of aromatic amino acids for the interaction with organic anion transporter OAT1: Implications for reducing the renal background in tumor imaging

説明

<p>The excellent tumor selectivity of amino acid-based imaging probes, [18F]FAMT (3-[18F]fluoro-a-methyl-l-tyrosine) and [123I]IMT (3-[123I]iodo-a-methyl-l-tyrosine), is supported by their selectivity for LAT1 (L-type amino acid transporter 1) which is specifically expressed in tumor cells. However, FAMT and IMT show a physiological background in kidney. Their renal accumulation is suppressed by probenecid, suggesting a contribution of organic anion transporter OAT1. To reveal the critical moieties responsible for the interaction with OAT1, we performed a structure-activity relationship analysis of aromatic amino acid derivatives in vitro. We revealed that both halogen and hydroxyl groups on the benzene ring are critical for the interaction with OAT1. Their positions on the benzene ring also affected the interaction. In contrast, the a-methyl moiety, which is essential for the selectivity to LAT1, was dispensable for the interaction with OAT1. These results hold a significant implication for designing not only the tumor-specific imaging probes with less renal background, but also the therapeutic agents for targeted radionuclide therapy with less adverse renal damage.</p>

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