Therapeutic effects of holmium-166 chitosan complex in rat brain tumor model

This study examined the effectiveness of Holmium-166 (Ho-166) chitosan complex therapy for a malignant glioma. Cultured C6 glioma cells (100,000 in 5 mu l) were injected into the caudate/putamen of 200 - 250 gram Wistar rats. Five days later, a Ho-166 chitosan complex was injected into the same site of the glioma injection. Four injection doses were administered: the control group received PBS 10 mu l, group 1 received an injection of 100 mu Ci (10 mu l), group 2 received an injection of 50 mu Ci (5 mu l), and group 3 received an injection of 10 mu Ci (1 mu l). The average tumor volume for each group was 1.385 mm(3) for the control group, 0.036 mm(3) for group 1, 0.104 mm(3) for group 2, and 0.111 mm(3) for group 3. Compared with the control group, the size of the tumors in groups 1, 2 and 3 was reduced by an average of 97.4%, 92.5% and 91.9%, respectively. The Kaplan-Meier survival curve of group 2 was the longest, followed by groups 3, group 1 and the control. The mean survival was 22.8, 59, 60, and 44.6 days for the control group and groups 3, 2 and 1, respectively. H-E staining revealed that group 2 yielded the best results in the destruction of the malignant glioma. TUNEL staining and immunohistochemical studies indicated apoptotic features. The Ho-166 chitosan complex proved to be effective in destroying the malignant glioma.