Feasibility study of C57BL/6 induced RM-1 cell line as a prostate cancer mice model for development of radiopharmaceuticals targeted prostate-specific membrane antigen (PSMA)

The preclinical study is an important stage in drug discovery and development. One of the keys to developing therapeutic methods is selecting an animal model that is suitable and capable of answering research questions. Animal models are required to develop cancer diagnostics and therapies, particularly for prostate cancer. Due to their ability as diagnostic and therapeutic tools, radiopharmaceuticals are one of the alternative therapies currently gaining significant interest. In this study, we generated a syngenic mice model of prostate cancer using C57BL/6 mice which have been subcutaneously injected with the RM-1 cell line (2 x 10^6 cells/100µL). The study’s findings revealed that tumours formed in all animals 14 days after injection with a diameter of 0.29±0.24 mm3. Histopathological analysis of tissue samples from normal, and tumour mice models were performed in this study to determine prostate-specific membrane antigen (PSMA) expression. The immunohistochemistry (IHC) staining with anti-hPSMA revealed a low expression of hPSMA in tumour tissue. This result was supported by a preliminary biodistribution study using Lutetium-177 PSMA, which has a low accumulation in tumour tissue (2.65±0.41 %ID/g). This low accumulation in tumour tissue supports the findings of IHC staining related to hPSMA expression in animal models. PSMA expression is known to be species-specific in tumour tissue and particular organ. In conclusion, the animal model of prostate cancer using C57BL/6 mice with RM-1 cell lines can be used for future studies requiring animal models without targeting specifically hPSMA. However, further investigation is needed to perform genetic transfection from hPSMA to cell line RM-1 so that cell line RM-1 could express PSMA type specific for humans.