title: In vivo labeling of amyloid with BF-108.
abstract: Detection of aggregated amyloid-beta (Abeta) 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 Abeta 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 Abeta aggregates in vitro and high lipophilicity. Intravenously administrated BF-108 labeled Abeta aggregates injected into the amygdala as observed under a fluorescence microscope, showing this compound's permeability of BBB and an ability to label Abeta 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.
authors.affiliation: Research Department, BF Research Institute, c/o National Cardiovascular Center, 7-1, 5-Chome, Fujishiro-dai, Suita, Osaka 565-0873, Japan. tsuemoto@silver.ocn.ne.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suemoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shiomitsu
authors.forename: Masako
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimadzu
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
authors.forename: Tohru
authors.initials: T
authors.lastname: Sawada
mesh_terms: D000166:Acridines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000345:Affinity Labels / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D016874:Neurofibrillary Tangles / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000378:metabolism
chemical_list: C483464:3-diethylamino-6-(2-fluoroethyl)ethylaminoacridine; D000166:Acridines; D000345:Affinity Labels; D000682:Amyloid; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D013844:Thiazoles; C009462:thioflavin T