Orthotopic pituitary tumors generated by stereotaxic GC cell injection in immunocompetent rats.

Innovative treatment strategies for pituitary tumors are necessary to limit the disease burden and to improve survival in cases of carcinomas. The paucity and inaccuracy of available preclinical models substantially hamper pituitary research and drug discovery. Hence, we describe a novel method to generate orthotopic pituitary tumors via stereotaxic injection of somatotroph GC cells into the pituitaries of immunocompetent Wistar Furth rats. Tumor growth was monitored by repeated 7 Tesla magnetic resonance imaging. The procedure consistently led to rapidly expanding intra- and suprasellar growth hormone-secreting tumors within their native anatomical environment. The generated tumors faithfully reproduced the microarchitecture of human somatotroph pituitary adenomas, including the immune infiltrates and other typical components of their microenvironment, which is a prerequisite for testing immunomodulating agents. This orthotopic model of proliferative pituitary tumors developed in immunocompetent hosts therefore unlocks new opportunities for preclinical studies.