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：

---

氟18放射性标记的荧光查尔酮的开发：评估检测糖原。

糖原是细胞产生的用于储存能量的葡萄糖的多支链多糖，在癌症中起关键作用。先前报道的荧光探针（CDg4）已显示在小鼠胚胎干细胞中选择性结合糖原，但是未在癌细胞中评估该分子。我们报告基于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。开发并合成了一种氟18放射性标记的CDg4（[18F] 5）衍生物，用于体内定量癌细胞中的总糖原水平，并在170分钟内合成，其无衰减校正的放射化学产率（RCY ndc）为5.1±0.9％ （n = 4）的放射化学纯度大于98％。体外评估了化合物5和[18F] 5结合糖原的潜力，但只有5个通过荧光显微镜显示有积累。测定5的积累是特异性的，因为在用α-淀粉酶消化碳水化合物聚合物时荧光信号减弱了。非放射性小鼠的PET成像突出显示[18F] 5的快速肝胆肠道消除，并在60分钟后在肝脏，血浆和尿液中几乎完全代谢降解，这通过放射性代谢物分析得以证实。通过荧光显微镜鉴定，荧光化合物5选择性地积累在含糖原的癌细胞中；然而，体内快速的代谢降解阻碍了[18F] 5作为PET放射性药物的进一步研究。非放射性小鼠的PET成像突出显示[18F] 5的快速肝胆肠道消除，并在60分钟后在肝脏，血浆和尿液中几乎完全代谢降解，这通过放射性代谢物分析得以证实。通过荧光显微镜鉴定，荧光化合物5选择性地积累在含糖原的癌细胞中；然而，体内快速的代谢降解阻碍了[18F] 5作为PET放射性药物的进一步研究。非放射性小鼠的PET成像突出显示[18F] 5的快速肝胆肠道消除，并在60分钟后在肝脏，血浆和尿液中几乎完全代谢降解，这通过放射性代谢物分析得以证实。通过荧光显微镜鉴定，荧光化合物5选择性地积累在含糖原的癌细胞中；然而，体内快速的代谢降解阻碍了[18F] 5作为PET放射性药物的进一步研究。