Glycomimetic drugs have attracted increasing interest as unique targeting vectors or surrogates for endogenous biomolecules. However, it is generally difficult to determine the in vivo pharmacokinetic profile of these compounds. In this work, two galectin-3 inhibitors were radiolabeled with fluorine-18 and used as surrogate PET tracers of TD139 and GB1107. Both compounds are promising drugs for clinical applications. In vivo evaluation revealed that both surrogates strongly differed with respect to their biodistribution profile. The disaccharide (TD139 surrogate) was rapidly eliminated from blood while the monosaccharide (GB1107 surrogate) showed no sign of excretion. The data obtained allowed us to infer the different in vivo fate of TD139 and GB1107 and rationalize how different administration routes could boost efficacy. Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides.

中文翻译：

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体内Veritas：18F放射性标记的糖代谢药可深入了解Galectin-3抑制剂的药理命运。

作为内源性生物分子的独特靶向载体或替代物，拟糖药物引起了越来越多的兴趣。但是，通常难以确定这些化合物的体内药代动力学特征。在这项工作中，两种Galectin-3抑制剂被氟18放射性标记，并用作TD139和GB1107的替代PET示踪剂。两种化合物都是用于临床的有前途的药物。体内评估显示，两种替代物的生物分布特征均存在很大差异。二糖（TD139替代物）从血液中迅速清除，而单糖（GB1107替代物）则没有排泄迹象。获得的数据使我们能够推断出TD139和GB1107在体内的不同命运，并合理化了不同的给药途径如何提高疗效。