Therapeutic efficacy and cell kinetics of intrathecal
ACNU, 3-(4-amino-2-methyl-5-pyrimidinyl) methyl-1-(2-chloroethyl)-1-nitrosourea, were investigated in experimental
meningeal carcinomatosis rats.
Therapeutic effect of intrathecal
ACNU (IT
ACNU) against
meningeal carcinomatosis model was evaluated in rats induced by intracisternal inoculation of Walker 256
carcinosarcoma cells. The median survival time of the rats treated with IT
ACNU 1.5 mg/kg on day 5 after
tumor inoculation was significantly increased by 145% as compared with that of non-treatment rats. The cell kinetics was studied immunohistochemically using indirect immunoperoxidase method with
bromodeoxyuridine (
BrdU) and anti-
BrdU monoclonal antibody (Becton-Dickinson). The
meningeal carcinomatosis rats were treated with IT
ACNU (1.5 mg/kg) on the fifth day after
tumor inoculation. Before and 12, 24, 48, 96 or 144 hours
after treatment, the rats received intravenous
BrdU (200 mg/kg) injection. Thirty minutes later, the rats were sacrificed and the brains were removed. Brain sections were stained immunohistochemically with anti-
BrdU monoclonal antibody. Labeling index (LI) which represented the percentage of
tumor cells in synthetic phase was obtained by counting immunoreactive cells under the microscope. Before treatment, LI was around 34% on day 5 after
tumor inoculation and dropped to below 20% 12 to 48 hours after IT
ACNU. However, it increased to around 36% on day 4 after IT
ACNU. The
antineoplastic effect of IT
ACNU against
meningeal carcinomatosis rats might be expected in the early stage of intrathecal administration.