Neutral metoclopramide sensitizes cytotoxicity induced by ionizing radiation in SCID mice xenografted with a human brain astrocytoma

Abstract

A formulation of metoclopramide (MCA) conformationally altered by neutralization of pH (nMCA, Neu‐Sensamide) has been shown to have the same efficacy of enhancing the cytotoxicity of a single dose of 1 Gy radiation as acidic formulations (e.g., Primperan, Sensamide) in a human lung adenocarcinoma (H2981) xenografted into SCID mice. In the present study, 2 × 1 Gy radiation was combined with 2 × 2 mg nMCA/kg body weight injected 2 hr before radiation treatment for evaluation of radiosensitization in SCID mice xenografted with a human brain astrocytoma (T24). Given in this treatment schedule, nMCA alone at 2 mg/kg showed no cytotoxic effect on tumor growth in vivo. When combined with 2 × 1 Gy of 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 efficiently as acidic MCA (aMCA) when analyzed 45 min after i.m. injection by high‐performance liquid chromatography. Int. J. Cancer 73:871–874, 1997. © 1997 Wiley‐Liss, Inc.