TY - JOUR
T1 - Acute toxicity of two Alzheimer's disease radiopharmaceuticals
T2 - FDDNP and IMPY
AU - Chang, Kang Wei
AU - Chen, Chia Chieh
AU - Lee, Shih Ying
AU - Wang, Hsin Ell
N1 - Funding Information:
This study was supported by the Department of Industrial Technology, Ministry of Economic Affairs (Taiwan, ROC). The authors are grateful to Dr. Cheng-Hsien Lin, Isotope Application Center, Institute of Nuclear Energy Research (INER), Longtan, Taoyuan, Taiwan (R. O. C). for guiding the information of the chemistry synthesis.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/10/1
Y1 - 2009/10/1
N2 - 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.
AB - 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.
KW - Alzheimers disease
KW - FDDNP
KW - IMPY
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=74049151575&partnerID=8YFLogxK
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U2 - 10.1080/01480540903127324
DO - 10.1080/01480540903127324
M3 - Article
C2 - 19793037
AN - SCOPUS:74049151575
SN - 0148-0545
VL - 32
SP - 429
EP - 437
JO - Drug and Chemical Toxicology
JF - Drug and Chemical Toxicology
IS - 4
ER -
