High-resolution positron emission microscopy of patient-derived tumor organoids

Syamantak Khan, June Ho Shin, Valentina Ferri, Ning Cheng, Julia E. Noel, Calvin Kuo, John B. Sunwoo and Guillem Pratx ()
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Syamantak Khan: Stanford University School of Medicine
June Ho Shin: Stanford University School of Medicine
Valentina Ferri: Stanford University School of Medicine
Ning Cheng: Stanford University School of Medicine
Julia E. Noel: Stanford University School of Medicine
Calvin Kuo: Stanford University School of Medicine
John B. Sunwoo: Stanford University School of Medicine
Guillem Pratx: Stanford University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract 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 18F-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 99mTc- 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.

Date: 2021
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DOI: 10.1038/s41467-021-26081-6

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