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

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.

Patient-derived cancer models: Valuable platforms for anticancer drug testing

“…Moreover, this technique demonstrated the potential to detect not only cytotoxic but also cytostatic activity (90). With the use of positron-emission microscopy was possible to establish that PDOs retain metabolic characteristics of parental tumours, indicating that this technique can be used to monitor responses in the organoid cultures (178). Even when the data obtained from preclinical models are not suitable to guide treatment decisions the information provided by these platforms might be precious to unveil mechanisms underlying drug resistances and develop strategies to restore or increase responsiveness to treatments (180,181).…”

“…These techniques however results PDOs death impairing sequential assessments (177). Emergent technologies such as label-free light microscopy and positron-emission microscopy have been tested to evaluate the antitumor activity of investigational agents in 3D cultures (90,178,179). Light microscopy might provide a more precise measurement of antitumor activity because it allows the evaluation of cell viability at single organoid level (90).…”

Brain organoids: Establishment and application

“…At present, various types of organoids have been successfully cultured in vitro , including brain organoids ( Lancaster et al, 2013 ; Paşca et al, 2015 ). And organoids have been applied to models of various cancers, including liver, breast, pancreatic, prostate, bladder, ovarian, and gastrointestinal cancers, and have also been used for the exploration of tumor development and drug resistance mechanisms ( Gao et al, 2014 ; Phillips, 2014 ; Khan et al, 2021 ). Therefore, the successful establishment of organoids is of great significance for GBM research.…”

Mimicking Tumor Metastasis Using a Transwell‐Integrated Organoids‐On‐a‐Chip Platform

“…Patient‐derived organoids (PDO) are miniature, 3D, self‐organized tissue culture models, that have been reported to more faithfully recapitulate characteristics of the original tumor compared with traditional cell lines. [ 11–14 ] Although tumor PDOs have seen tremendous progress in patient‐specific testing of clinical and emerging anticancer treatments, in vitro metastasis evaluation in organoid platforms remains absent. For example, traditional methods for detecting cell migration, such as Transwell and cell scratch, are unable to mimic the intravasation activity of original tumors.…”