Department of Radiation Oncology, Division of Medical Physics, Stanford University School of Medicine, Stanford, USA.
Department of Otolaryngology, Division of Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Nat Commun. 2021 Oct 7;12(1):5883. doi: 10.1038/s41467-021-26081-6.
Tumor organoids offer new opportunities for translational cancer research, but unlike animal models, their broader use is hindered by the lack of clinically relevant imaging endpoints. Here, we present a positron-emission microscopy method for imaging clinical radiotracers in patient-derived tumor organoids with spatial resolution 100-fold better than clinical positron emission tomography (PET). Using this method, we quantify F-fluorodeoxyglucose influx to show that patient-derived tumor organoids recapitulate the glycolytic activity of the tumor of origin, and thus, could be used to predict therapeutic response in vitro. Similarly, we measure sodium-iodine symporter activity using Tc- pertechnetate and find that the iodine uptake pathway is functionally conserved in organoids derived from thyroid carcinomas. In conclusion, organoids can be imaged using clinical radiotracers, which opens new possibilities for identifying promising drug candidates and radiotracers, personalizing treatment regimens, and incorporating clinical imaging biomarkers in organoid-based co-clinical trials.
肿瘤类器官为转化癌症研究提供了新的机会，但与动物模型不同的是，由于缺乏临床相关的影像学终点，其更广泛的应用受到了阻碍。在这里，我们提出了一种正电子发射显微镜方法，用于对患者来源的肿瘤类器官中的临床放射性示踪剂进行成像，其空间分辨率比临床正电子发射断层扫描（PET）高出 100 倍。使用这种方法，我们定量测量 F-氟脱氧葡萄糖的流入，以表明患者来源的肿瘤类器官再现了起源肿瘤的糖酵解活性，因此，可用于体外预测治疗反应。同样，我们使用 Tc-高锝酸盐测量钠碘同向转运体的活性，发现碘摄取途径在甲状腺癌衍生的类器官中是功能保守的。总之，临床放射性示踪剂可用于对类器官进行成像，这为鉴定有前途的候选药物和放射性示踪剂、制定个体化治疗方案以及将临床影像学生物标志物纳入基于类器官的临床试验提供了新的可能性。
