TY - JOUR
T1 - In vivo labeling of amyloid with BF-108
AU - Suemoto, Takahiro
AU - Okamura, Nobuyuki
AU - Shiomitsu, Tsuyoshi
AU - Suzuki, Masako
AU - Shimadzu, Hiroshi
AU - Akatsu, Hiroyasu
AU - Yamamoto, Takayuki
AU - Kudo, Yukitsuka
AU - Sawada, Tohru
PY - 2004/1
Y1 - 2004/1
N2 - Detection of aggregated amyloid-beta (Aβ) with a non-invasive imaging modality such as positron emission tomography (PET) was suggested to be ideal for the diagnosis of Alzheimer's disease (AD) prior to the onset of clinical symptoms. We have been searching for imaging probe candidates with a high affinity for aggregated Aβ in vitro and in vivo and high lipophilicity, a characteristic that allows for the permeation of the blood-brain barrier (BBB). As analyzed by Thioflavin T (ThT) assay and octanol/water partition coefficient test (PC), 3-diethylamino-6-(2-fluoroethyl)ethylaminoacridine (BF-108) were found to have high affinity for Aβ aggregates in vitro and high lipophilicity. Intravenously administrated BF-108 labeled Aβ aggregates injected into the amygdala as observed under a fluorescence microscope, showing this compound's permeability of BBB and an ability to label Aβ in vivo. BF-108 also labeled neuritic senile plaques (SPs), neurofibrillary tangles, and amyloid-laden vessels in temporal and hippocampal sections from AD patients. Following intravenous administration of BF-108 to an APP23 transgenic (TG) mouse, in vivo labeling of endogenous plaques was seen in brain sections by fluorescence microscopy. These properties suggest the potential utility of BF-108 for in vivo imaging of AD pathology.
AB - Detection of aggregated amyloid-beta (Aβ) with a non-invasive imaging modality such as positron emission tomography (PET) was suggested to be ideal for the diagnosis of Alzheimer's disease (AD) prior to the onset of clinical symptoms. We have been searching for imaging probe candidates with a high affinity for aggregated Aβ in vitro and in vivo and high lipophilicity, a characteristic that allows for the permeation of the blood-brain barrier (BBB). As analyzed by Thioflavin T (ThT) assay and octanol/water partition coefficient test (PC), 3-diethylamino-6-(2-fluoroethyl)ethylaminoacridine (BF-108) were found to have high affinity for Aβ aggregates in vitro and high lipophilicity. Intravenously administrated BF-108 labeled Aβ aggregates injected into the amygdala as observed under a fluorescence microscope, showing this compound's permeability of BBB and an ability to label Aβ in vivo. BF-108 also labeled neuritic senile plaques (SPs), neurofibrillary tangles, and amyloid-laden vessels in temporal and hippocampal sections from AD patients. Following intravenous administration of BF-108 to an APP23 transgenic (TG) mouse, in vivo labeling of endogenous plaques was seen in brain sections by fluorescence microscopy. These properties suggest the potential utility of BF-108 for in vivo imaging of AD pathology.
KW - Alzheimer's disease
KW - Amyloid-beta
KW - Imaging diagnostic probe
KW - Positron emission tomography
KW - Senile plaque
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U2 - 10.1016/j.neures.2003.09.005
DO - 10.1016/j.neures.2003.09.005
M3 - Article
C2 - 14687882
AN - SCOPUS:0346365503
VL - 48
SP - 65
EP - 74
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
IS - 1
ER -