Safety and efficacy of convection-enhanced delivery of ACNU, a hydrophilic nitrosourea, in intracranial brain tumor models

Shin Ichiro Sugiyama, Yoji Yamashita, Toshio Kikuchi, Ryuta Saito, Toshihiro Kumabe, Teiji Tominaga

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Convection-enhanced delivery (CED) is a local infusion technique, which delivers chemotherapeutic agents directly to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED distribution is significantly increased if the infusate is hydrophilic. This study evaluated the safety and efficacy of CED of nimustine hydrochloride:3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl) -1-nitrosourea hydrochloride (ACNU), a hydrophilic nitrosourea, in rat 9 L brain tumor models. The local neurotoxicity of ACNU delivered via CED was examined in normal rat brains, and the maximum tolerated dose (MTD) was estimated at 0.02 mg/rat. CED of ACNU at the MTD produced significantly longer survival time than systemic administration (P < 0.05, log-rank test). Long-term survival (80 days) and eradication of the tumor occurred only in the CED-treated rats. The tissue concentration of ACNU was measured by high-performance liquid chromatography, which revealed that CED of ACNU at the dose of 100-fold less total drug than intravenous injection carried almost equivalent concentrations of ACNU into rat brain tissue. CED of hydrophilic ACNU is a promising strategy for treating brain tumors.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalJournal of Neuro-Oncology
Volume82
Issue number1
DOIs
Publication statusPublished - 2007 Mar

Keywords

  • Brain tumor
  • Convection-enhanced delivery
  • High-performance liquid chromatography
  • Nimustine hydrochloride
  • Nitrosourea

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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