Novel Antitumor Effect of Carboplatin Delivered by Intracerebral Microinfusion in a Rat Malignant Glioma Model

Carboplatin loaded osmotic mini-pumps were implanted in 24 9L malignant glioma-bearing rats to investigate the implications of direct intracerebral microinfusion. Carboplatin using 0.1 mg/ml (low dose group) or 1.0 mg/ml (high dose group) with eight rats in each group, or 5% D-glucose (control group) in eight rats were infused at 1 μl/hr for 7 days. The tumor volume was serially measured by magnetic resonance (MR) imaging with gadolinium as the enhanced area, and the survival periods and histological findings were also examined. Separately, to examine the effects of intracerebral carboplatin infusion on vascular permeability, tumor-bearing rats received intravenous administration of 2% Evans blue at 21 days after infusion. The high dose group showed transient increase of enhanced volume at 21 days associated with mass effect, and significantly decreased tumor volume at 28 and 3 5 days compared with the control and low dose groups. The high dose group showed significant longer survival time than the control and low dose groups. Histological examination of the high dose group at 21 days showed the central tumor necrotic area around the infusion site and Evans blue leakage into the surrounding enhanced rim and the necrotic core. Therefore, leakage of plasma fluid into the necrotic area was considered to be the cause of apparent transient swelling. The present study demonstrated quantitatively using MR imaging that intracerebral carboplatin microinfusion significantly inhibited the rapid growth of experimental rat glioma but that the high dose required carries the risk of transient swelling of the target tumor.