Acute toxicity of two Alzheimer's disease radiopharmaceuticals: FDDNP and IMPY

Kang Wei Chang, Chia Chieh Chen, Shih Ying Lee, Hsin Ell Wang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that results in memory deficits. The effect of AD is the leading cause of dementia in the United States and constitutes a burgeoning public health problem. AD is characterized by the presence of two aberrant structures, senile plaques, and neurofibrillary tangles, present in the brain of the patients. [18F]FDDNP and [ 123I]IMPY were developed for the early diagnosis of AD by Dr. J. Barrios and Dr. H. Kung, respectively. These two radiotracers could bind with the amyloid location site in the AD patient brain. The aim of this study was to analyze the acute single toxic effects dose of two nonradiochemical labeled compounds in rats. Animals were injected from the tail vein with nonlabeled-FDDNP (05mg/kg) and nonlabeled-IMPY (0-300μg/kg), respectively, and observed for 2 weeks. These doses provide safety margins of 35,000- to 140-fold and 1,000- to 100-fold over the maximal recommend human dose (0.1mg/70kg) and (20μg/60kg) (by FDDNP and IMPY), respectively. With IMPY, there were no changes in mortality, clinical situation, and gross necropsy. With FDDNP, the high dose (5mg/kg) produced mortality in 2 of 5 and 1 of 5 in male and female rats, respectively. The high dose of FDDNP showed liver damage in dying animals. No other adverse toxic effects at dose levels up to 1.0mg/kg of FDDNP were noted. FDDNP exerted no adverse toxic effects in rats given doses up to 1mg/kg and IMPY at the dose levels up to 300 μg/kg.

Original languageEnglish
Pages (from-to)429-437
Number of pages9
JournalDrug and Chemical Toxicology
Volume32
Issue number4
DOIs
Publication statusPublished - Oct 1 2009
Externally publishedYes

Keywords

  • Alzheimers disease
  • FDDNP
  • IMPY
  • Toxicity

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis
  • Chemical Health and Safety

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