11C-labelled PIB analogues as potential tracer agents for in vivo imaging of amyloid beta in Alzheimer's disease.
Pittsburgh Compound-B (PIB) is currently being evaluated clinically for in vivo visualization of amyloid plaques in patients with Alzheimer's disease (AD). We have synthesized three structural isomers of 6-hydroxy-2-(4'-aminophenyl)-1,3-benzothiazole, performed radiolabelling with carbon-11 and investigated their in vivo and in vitro properties. Specific binding to amyloid plaques was demonstrated in vitro using post-mortem brain homogenates of AD patients, transgenic AD mice brain sections and post-mortem human AD brain sections. In normal mice, initial brain uptake (at 2 min p.i.) was high and was followed by a fast wash-out. The three structural analogues have a high potential as tracer agents for in vivo visualization of amyloid plaques in AD patients.
Serdons
K
K
Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, K.U. Leuven, O&N2, Herestraat 49-Bus 821, 3000 Leuven, Belgium. kim.serdons@pharm.kuleuven.be
Verduyckt
T
T
Vanderghinste
D
D
Borghgraef
P
P
Cleynhens
J
J
Van Leuven
F
F
Kung
H
H
Bormans
G
G
Verbruggen
A
A
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D006878:Hydroxides / Q000737:chemistry; D007536:Isomerism; D051379:Mice; D011849:Radioactive Tracers; D013194:Staining and Labeling; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D006878:Hydroxides; D011849:Radioactive Tracers; D013844:Thiazoles; C031356:hydroxide ion; C005465:benzothiazole