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Eur Thyroid J. 2025 Aug 18:ETJ-24-0405. doi: 10.1530/ETJ-24-0405. Online ahead of print.
ABSTRACT
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. Function measurements showed the production of calcitonin and CEA. Interpretation of the preliminary experiments with TKIs and PET tracers were limited by sample size but demonstrate 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.
PMID:40823969 | DOI:10.1530/ETJ-24-0405