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

✍ Scribed by Jianyi Hua; Anders R. Olsson; Ronald W. Pero

• Book ID: 101234593
• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 62 KB
• Volume: 73
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19971210)73:6<871::aid-ijc18>3.0.co;2-7

✦ Synopsis

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.