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

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。

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.