Abstract: PURPOSE: To construct a brachytherapentic model of patient-derived salivary gland malignant tumor organoids, and evaluate the impact of ¹²⁵I radioactive seeds intervention on the activity of different organoids, and explore the feasibility of using this model to guide clinical personalized treatment of salivary gland malignant tumors. METHODS: Biopsy specimens from patients with malignant salivary gland tumors including mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma(ACC) and acinic cell carcinoma (AciCC) from Xuzhou Central Hospital were collected, and 3D culture method was used to construct the organoid model. The expression levels of immunohistochemical indicators in salivary gland malignant tumor tissue samples and organoid samples were detected. Brachytherapentic model was constructed and the effect of different doses of ¹²⁵I seeds on organoid activity were detected using 3D cell viability assay. The activity curves were plotted and the IC₅₀ values were calculated. The data were analyzed by GraphPad Prism 9.0 software. RESULTS: H-E staining results and immunohistochemical staining results identified homology between organoids and specimen tumors. The mean IC₅₀ values of ¹²⁵I seeds on 5 cases of salivary gland malignant tumor organoids (1 case of ACC, 2 cases of AciCC and 2 cases of MEC) were 8 508, 6 053, 5 203, 10 379 and 7 743 cGy, respectively. AciCC has a higher sensitivity to ¹²⁵I seeds, and the sensitivity of ¹²⁵I seeds varied among individuals of the same type of tumor. CONCLUSIONS: An in vitro tumor organoid culture platform has been established for specimens from patients with salivary gland malignant tumors, and its morphological, histological structure, and molecular marker expression are consistent with the characteristics of tumor cells in the original specimens. Intervention results indicated that the model has significant individualized differences, providing a theoretical basis and methodological reference for the effectiveness of ¹²⁵I seeds in some patients with local, recurrent, advanced, poorly differentiated, or unresectable tumours. This model has the advantages of low cost, short modeling time, and high throughput detection. It can predict the patient's post-treatment response in vitro, guide risk assessment of malignant tumors in clinical practice, and establish personalized and precise treatment plans.

Key words: Organoid, Salivary gland malignant tumor, ¹²⁵I radioactive seed, Anticancer activity