Antitumor effect of intra-arterial tumor necrosis factor-α in rats with transplanted intracerebral glioma and its evaluation by MRI

Recombinant human TNF-α was administered intraarterially to rats with transplanted intracerebral glioma, 1 x 10⁶ of T9 rat glioma cell were transplanted into Fisher 344 rat brain stereotaxically and 1000units of TNF- α was administered at a rate of 100 μl/min, via an internal carotid artery 1 or 3 weeks after the transplantation. The effects of TNF-α were evaluated by MRI and histopathological examinations. Neurological symptoms, i.e., hemiparesis, appeared after 9.0±0.63 days and all rats died of tumor overloading 14.5±0.84 days after the transplantation. Single injection of TNF-α on 7th day after the transplantation induced regression of the tumor size in one of six rats. The tumors were detected 3 days after transplantation by MRI and they were revealed as low/iso intensity mass in T1W1, iso/high intensity in T2W1, and were enhanced by Gd-DTPA heterogeneously. On 7/14 days after the transplantation, the tumor grew approximately 7/10mm in diameter. The single 1000 units of TNF-α were administered via an internal carotid artery. 3 days after the administration of TNF-α, regression of the tumor size was seen in one of six rats and decrease of peritumoral edema was seen in three. These effects of TNF-α were, however, transient and they were not demonstrated on day 7. Single injection of TNF-α was not effective for large tumors more than 10mm in diameter seen 14 days after the transplantation. These data suggest that intra-arterial TNF-α should be administered at an early stage of the tumor growth and several injections are needed to cause regression in the size of the gliomas.