NEUTRAL METOCLOPRAMIDE SENSITIZES CYTOTOXICITY INDUCED BY IONIZING-RADIATION IN SCID MICE XENOGRAFTED WITH A HUMAN BRAIN ASTROCYTOMA

A formulation of metoclopramide (MCA) conformationally altered by neut ralization of pH (nMCA, Neu-Sensamide) has been shown to have the same efficacy of enhancing the cytotoxicity of a single dose of 1 Gy radia tion as acidic formulations (e.g., Primperan, Sensamide) in a human lu ng adenocarcinoma (H2981) xenografted into SCID mice. In the present s tudy, 2 x 1 Gy radiation was combined with 2 x 2 mg nMCA/kg body weigh t injected 2 hr before radiation treatment for evaluation of radiosens itization in SCID mice xenografted with a human brain astrocytoma (T24 ). Given in this treatment schedule, nMCA alone at 2 mg/kg showed no c ytotoxic effect on tumor growth in vivo. When combined with 2 x 1 Gy o f radiation, however, the cytotoxicity was significantly increased as measured by tumor growth delay over the radiation-only-treated group. Furthermore, nMCA was absorbed into brains of mice and rats as efficie ntly as acidic MCA (aMCA) when analyzed 45 min after i.m. injection by high-performance liquid chromatography. (C) 1997 Wiley-Liss, Inc.