Analysis of gastrointestinal behavior and the prediction of the absorption rate of orally administered drugs using PET molecular imaging technology

利用PET分子影像技术分析胃肠行为并预测口服药物的吸收率

• 批准号: 23790214
• 负责人: TAKASHIMA Tadayuki
• 金额: $ 2.83万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790214/
• 关键词: 分子イメージング; Positron Emission Tomography(PET); 消化管吸収; PET

In this study, we investigated the gastrointestinal (GI) behavior of PET probes derived from drugs and its analog with the different physicochemical properties. The GI behavior of our original PET probes, [^<11>C]dehydropravastatin, an organic anion PET probe, and [^<11>C]metformin, an organic cation PET probe, were compared by the PET image analysis. In addition, PET image analysis was performed using [^<18>F]deoxyfluoropoly (ethyleneglycol)s ([^<18>F]FPEG), as a non-absorbable marker to elaborate on more detail of the GI physiology, such as a segmental transition of the administered water and fluid volume and distribution in the intestine. The rate constant of the intestinal transition of radioactivity in each intestinal segment was calculated by the kinetic model analysis, which revealed that PET analysis allows to determine the GI transit from the same individuals and that it is applicable to determine the site specific intestinal absorption. In conclusion, we demonstrated the high potency of PET imaging technique to elucidate the distribution of orally administered solution in the GI tract in experimental animal study.

本研究主要研究了不同理化性质药物及其类似物的PET探针的胃肠道行为。通过PET图像分析比较了我们的原始PET探针、[^<11>C]脱氢普伐他汀（一种有机阴离子PET探针）和[^<11>C]二甲双胍（一种有机阳离子PET探针）的GI行为。此外，使用[^<18>F]脱氧氟聚（乙二醇）（[^<18>F]FPEG）作为不可吸收的标记物进行PET图像分析，以详细说明GI生理学的更多细节，例如肠内给药水和液体体积和分布的节段性转变。通过动力学模型分析计算每个肠段中放射性的肠转运速率常数，这表明PET分析可以确定相同个体的GI转运，并且适用于确定部位特异性肠吸收。总之，我们证明了PET成像技术在动物实验研究中阐明口服给药溶液在胃肠道中分布的高效力。

项目成果

PET を用いた非吸収性マーカー経口投与後の消化管内挙動の解析

使用 PET 分析口服不可吸收标记物后的胃肠行为

• 发表时间: 2012
• 作者: 高島忠之;新垣友隆;片山由美子;尾崎大起;馬渡彩;片岡誠;林中恵美;和田康弘;石田翔;畑中剣太朗;土居久志;鈴木正昭;赤井周司;奥直人;山下伸二;渡辺恭良
• 通讯作者: 渡辺恭良