A large-animal model was developed to facilitate the noninvasive investigation of the effect on the human glioma-derived D-54 MG (glioblastoma multiforme) continuous cell line of a variety of therapeutic regimens. Twenty random-bred male cats were inoculated intracerebrally with 1 × 107 D-54 MG tumor cells after being initiated on one of three preparatory regimens of cyclosporin A p.o. Reproducible success of D-54 MG xenotransplantation (100%, 6 of 6 cats) was achieved only after pretreatment with 120 mg cyclosporin A p.o. (24–30 mg/kg) daily for ≥10 days prior to tumor implantation. High-performance liquid chromatography-derived whole blood cyclosporin A 12-h trough levels of ≥640 ng/ml were seen in successful implants. Lesions ranging from 2 to 20 mm in diameter were seen in cats sacrificed 27–44 days after implantation with no growth seen in control animals.
Histopathological examination revealed the tumors to be well-circumscribed anaplastic intracerebral tumors with some invasion into surrounding host parenchyma. Perivascular lymphocytic cuffing was observed, but intratumoral lymphocytic infiltration was minimal. Gadolinium-EDTA-enhanced nuclear magnetic resonance imaging provided accurate tumor localization in T1-weighted images (TE 26 ms; TR 600 ms). Biochemical tests of kidney, liver, and hematological function were within normal limits, although 10% (2 of 20) of the animals developed gingival hyperplasia, and 5% (1 of 20) developed intussusception.
The reproducible growth of the D-54 MG human glioblastoma cell line in a large-animal model eliminates many of the limitations associated with the standard nude mouse/rat model, thereby providing a novel test bed for a variety of imaging modalities as well as for drug immunoconjugate localization and toxicity studies.
Supported by Alberta Cancer Board Grant RIP 18 and the Alberta Heritage Foundation for Medical Research (B. W. K.)