Glycogen is a multibranched polysaccharide of glucose produced by cells to store energy and plays a key role in cancer. A previously reported fluorescent probe (CDg4) was shown to selectively bind glycogen in mouse embryonic stem cells, however the molecule was not evaluated in cancer cells. We report the synthesis and biological evaluation of a dual-modality imaging probe based on CDg4, for positron emission tomography (PET) and fluorescence microscopy. A fluorine-18 radiolabelled derivative of CDg4, ([18F]5) for in vivo quantification of total glycogen levels in cancer cells was developed and synthesised in 170 min with a non-decay corrected radiochemical yield (RCY n.d.c) of 5.1 ± 0.9% (n = 4) in > 98% radiochemical purity. Compound 5 and [18F]5 were evaluated in vitro for their potential to bind glycogen, but only 5 showed accumulation by fluorescence microscopy. The accumulation of 5 was determined to be specific as fluorescent signal diminished upon the digestion of carbohydrate polymers with α-amylase. PET imaging in non-tumour bearing mice highlighted rapid hepato-biliary-intestinal elimination of [18F]5 and almost complete metabolic degradation after 60 min in the liver, plasma and urine, confirmed by radioactive metabolite analysis. Fluorescent compound 5 selectively accumulated in glycogen containing cancer cells, identified by fluorescence microscopy; however, rapid in vivo metabolic degradation precludes further investigation of [18F]5 as a PET radiopharmaceutical.

中文翻译：

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氟 18 放射性标记荧光查尔酮的开发：评估用于检测糖原。


糖原是细胞产生的多支链葡萄糖多糖，用于储存能量，在癌症中发挥着关键作用。先前报道的荧光探针（CDg4）被证明可以选择性地结合小鼠胚胎干细胞中的糖原，但该分子并未在癌细胞中进行评估。我们报告了基于 CDg4 的双模态成像探针的合成和生物学评估，用于正电子发射断层扫描 (PET) 和荧光显微镜。用于体内定量癌细胞总糖原水平的 CDg4 氟 18 放射性标记衍生物 ([18F]5) 开发并在 170 分钟内合成，其非衰变校正放射化学产率 (RCY ndc) 为 5.1 ± 0.9% (n = 4) 放射化学纯度 > 98%。在体外评估了化合物 5 和 [ 18 F] 5 结合糖原的潜力，但只有 5 种通过荧光显微镜显示出积累。 5 的积累被确定为特异性的，因为用 α-淀粉酶消化碳水化合物聚合物时荧光信号减弱。非荷瘤小鼠的 PET 成像强调 [18F]5 快速肝胆肠消除，60 分钟后在肝脏、血浆和尿液中几乎完全代谢降解，经放射性代谢物分析证实。通过荧光显微镜鉴定，荧光化合物5选择性地积聚在含糖原的癌细胞中；然而，快速的体内代谢降解阻碍了[18F]5作为PET放射性药物的进一步研究。