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.

Highlights

  • 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

  • Tumor organoids were seeded from processed surgical samples of head-and-neck cancer patients and cultured in basement membrane extract (BME), a soluble form of basement membrane purified from Engelbreth-Holm-Swarm tumor

  • A specialized culture medium (EN medium) containing Dulbecco’s Modified Eagle Medium (DMEM)/F-12 supplemented with 10% Noggin-conditioned media, Nicotinamide (10 mM), Nacetylcysteine (1 mM), B-27 minus vitamin A (1×), Pen–Strep (1×), and EGF (50 ng/mL) was used to grow organoids

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Summary

Introduction

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. 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). 1234567890():,; Patient-derived tumor organoids are miniature, threedimensional, self-organized tissue culture models that are derived from primary patient tumor cells and studied in the laboratory[1,2] These organoid cultures closely recapitulate the genetic and morphological heterogeneity, stromal components, and microenvironment of the original tumor[1,2,3,4,5,6,7,8,9,10].

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