title: Amyloid imaging probes are useful for detection of prion plaques and treatment of transmissible spongiform encephalopathies.
abstract: Diagnostic imaging probes have been developed to monitor cerebral amyloid lesions in patients with neurodegenerative disorders. A thioflavin derivative, 2-[4'-(methylamino)phenyl] benzothiazole (BTA-1) and a Congo red derivative, (trans, trans),-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) are representative chemicals of these probes. In this report, the two chemicals were studied in transmissible spongiform encephalopathies (TSE). Both BTA-1 and BSB selectively bound to compact plaques of prion protein (PrP), not only in the brain specimens of certain types of human TSE, but also in the brains of TSE-infected mice when the probes were injected intravenously. The chemicals bound to plaques in the brains were stable and could be detected for more than 42 h post-injection. In addition, the chemicals inhibited abnormal PrP formation in a cellular model of TSE with IC(50) values of 4 nM for BTA-1 and 1.4 micro M for BSB. In an experimental mouse model, the intravenous injection of 1 mg BSB prolonged the incubation period by 14 %. This efficacy was only observed against the RML strain and not the other strains examined. These observations suggest that these chemicals bind directly to PrP aggregates and inhibit new formation of abnormal PrP in a strain-dependent manner. Both BTA-1 and BSB can be expected to be lead chemicals not only for imaging probes but also for therapeutic drugs for TSEs caused by certain strains.
authors.affiliation: Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Doh-Ura
authors.affiliation: BF Research Institute Inc., Osaka 565-0873, Japan.
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Department of Bacteriology, Nagasaki University School of Medicine, Nagasaki, 852-8501, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Murakami-Kubo
authors.affiliation: Department of Laboratory Medicine, Kumamoto University, Kumamoto 860-0081, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.affiliation: BF Research Institute Inc., Osaka 565-0873, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Sawada
authors.affiliation: Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Iwaki
mesh_terms: D000682:Amyloid / Q000032:analysis*; D000818:Animals; D006801:Humans; D051379:Mice; D017096:Prion Diseases / Q000175:diagnosis*; D011328:Prions / Q000032:analysis* / Q000037:antagonists & inhibitors
chemical_list: D000682:Amyloid; D011328:Prions