Imaging Biotin Trafficking In Vivo with Positron Emission Tomography

The water-soluble vitamin biotin is essential for cellular growth, development, and well-being, but its absorption, distribution, metabolism, and excretion are poorly understood. This paper describes the radiolabeling of biotin with the positron emission tomography (PET) radionuclide carbon-11 ([11C]­biotin) to enable the quantitative study of biotin trafficking in vivo. We show that intravenously administered [11C]­biotin is quickly distributed to the liver, kidneys, retina, heart, and brain in rodentsconsistent with the known expression of the biotin transporterand there is a surprising accumulation in the brown adipose tissue (BAT). Orally administered [11C]­biotin was rapidly absorbed in the small intestine and swiftly distributed to the same organs. Preadministration of nonradioactive biotin inhibited organ uptake and increased excretion. [11C]­Biotin PET imaging therefore provides a dynamic in vivo map of transporter-mediated biotin trafficking in healthy rodents. This technique will enable the exploration of biotin trafficking in humans and its use as a research tool for diagnostic imaging of obesity/diabetes, bacterial infection, and cancer.

水溶性维生素生物素（biotin）是细胞生长、发育及维持机体健康所必需的物质，但其吸收、分布、代谢与排泄过程目前尚未得到充分阐释。本文报道了利用正电子发射断层扫描（positron emission tomography, PET）放射性核素碳-11对生物素进行放射性标记，制备得到[11C]生物素，以此实现生物素体内转运过程的定量研究。研究显示，经静脉给药的[11C]生物素可快速分布于啮齿类动物的肝脏、肾脏、视网膜、心脏与脑部，这与已知的生物素转运蛋白表达分布特征一致，且在棕色脂肪组织（brown adipose tissue, BAT）中存在出人意料的蓄积。经口给药的[11C]生物素可在小肠内快速吸收，并迅速分布至上述器官组织。预先给予非放射性生物素可抑制各器官对标记物的摄取并增加其排泄量。因此，[11C]生物素正电子发射断层扫描成像技术可实现健康啮齿类动物体内转运蛋白介导的生物素转运过程的动态在体成像。该技术将为人类生物素转运过程的研究提供全新途径，同时可作为研究工具，应用于肥胖/糖尿病、细菌感染及癌症的诊断成像相关研究。