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Updated: Aug 15, 2026

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Published on: February 17, 2023
Patient-derived medullary thyroid cancer organoids: a potential model for mechanistic studies on diagnostics and
Eline C Jager1,2, Luc H J Sondorp1,3, Rufina Maturi3,4
1Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Objective:
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine thyroid tumor, with only 30 new patients annually in the Netherlands. PET imaging provides information on distant metastases, after which tyrosine kinase inhibitors (TKIs) may be initiated. The rarity of the disease impedes large controlled trials, and therefore the challenge of selecting the best TKI and PET tracer for individual patients persists. To explore whether an in vitro model could be developed to guide the selection of appropriate PET tracers or TKI therapies in the future, we aimed to establish an MTC organoid model for the first time.
Methods:
Dispersed cells from MTC biopsies were suspended in Matrigel, allowing organoid formation. The self-renewal potential was tested by dissociation and re-plating cells and determining organoid-forming efficiency. MTC-specific gene and protein expression were characterized by qPCR and immunofluorescent staining. Moreover, MTC-organoids (MTOs) were exposed to TKIs and PET tracers in proof-of-principle experiments.
Results:
Ten MTC biopsies were processed and successfully cultured as MTOs. MTC-derived cells showed self-renewal potency for several passages, indicating the presence of putative stem cells. Gene and protein expression of MTC-specific markers in tissue and MTOs, and function measurements showed the production of calcitonin and CEA. Interpretation of the preliminary experiments with TKIs and PET tracers was limited by sample size but demonstrates their future potential.
Conclusion:
We were able to culture MTC organoids that resemble the original tissue in gene expression, protein expression, and functionality. However, international, multi-center studies are required to meet the standards for future clinical applications.
Insights
Researchers developed a novel medullary thyroid carcinoma (MTC) organoid model from patient biopsies. This MTC organoid model shows potential for guiding personalized PET tracer and tyrosine kinase inhibitor (TKI) selection in rare cancer treatment.
Area of Science:
- Oncology
- Biotechnology
- Molecular Biology
Background:
- Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor, posing challenges for clinical trials and personalized treatment selection.
- Current treatment decisions for MTC, including tyrosine kinase inhibitors (TKIs) and PET imaging, are often hindered by the disease's rarity.
Purpose of the Study:
- To establish the first in vitro medullary thyroid carcinoma organoid model.
- To explore the potential of this organoid model for guiding the selection of personalized PET tracers and TKI therapies.
Main Methods:
- Medullary thyroid carcinoma organoids (MTOs) were generated from patient biopsies using Matrigel culture.
- Self-renewal potential was assessed, and MTC-specific gene and protein expression (calcitonin, CEA) were characterized.
- Proof-of-principle experiments involved exposing MTOs to TKIs and PET tracers.
Main Results:
- Successful culture of MTC organoids from ten patient biopsies, demonstrating self-renewal capacity.
- MTOs maintained MTC-specific gene and protein expression and functionality, including calcitonin and CEA production.
- Preliminary TKI and PET tracer experiments showed potential, though limited by sample size.
Conclusions:
- Medullary thyroid carcinoma organoids were successfully established, mirroring the original tissue's characteristics.
- The MTC organoid model holds promise for future clinical applications in personalized therapy selection.
- Further international, multi-center studies are necessary to validate these findings for clinical use.

