TY - JOUR
T1 - Development of novel amyloid imaging agents based upon thioflavin S
AU - Wei, Jingjun
AU - Wu, Chunying
AU - Lankin, David
AU - Gulrati, Anil
AU - Valyi-Nagy, Tibor
AU - Cochran, Elizabeth
AU - Pike, Victor W.
AU - Kozikowski, Alan
AU - Wang, Yanming
PY - 2005/4/1
Y1 - 2005/4/1
N2 - To date, small-molecule amyloid-imaging agents for in vivo detection and quantitation of amyloid deposits in Alzheimer's disease (AD) have been developed and successfully applied to human subjects. Preliminary studies have indicated that these amyloid-imaging agents were accumulated in the AD brains in a pattern that is relatively consistent with AD pathology, at least in the regions of amyloid-rich grey matter. These studies have also proven the concept that amyloid dyes, normally too hydrophilic to enter the brain, can be chemically modified to enhance brain permeability, binding affinity, as well as improve binding specificity for amyloid deposits. Related studies have suggested that structurally different agents can be developed that bind to different sites on amyloid deposits. In fact, in vivo cross-referencing studies based upon different amyloid-imaging agents may permit better characterization of AD pathology. But more importantly, novel amyloid imaging agents are required that will allow direct correlation between the results of animal models and human subjects based upon identical imaging modalities. Thus far, amyloid stains such as Congo red and thioflavin T have been extensively studied. However, another widely used amyloid dye, thioflavin S, has not been previously explored. This is in part due to the fact that thioflavin S exists as a mixture, not a pure chemical entity, albeit that the major component has been characterized. We hypothesized that neutral analogs, based upon the major component, could be developed as novel amyloid imaging agents, that exhibit complementary binding properties and pharmacokinetic profiles compatible with potential human studies.
AB - To date, small-molecule amyloid-imaging agents for in vivo detection and quantitation of amyloid deposits in Alzheimer's disease (AD) have been developed and successfully applied to human subjects. Preliminary studies have indicated that these amyloid-imaging agents were accumulated in the AD brains in a pattern that is relatively consistent with AD pathology, at least in the regions of amyloid-rich grey matter. These studies have also proven the concept that amyloid dyes, normally too hydrophilic to enter the brain, can be chemically modified to enhance brain permeability, binding affinity, as well as improve binding specificity for amyloid deposits. Related studies have suggested that structurally different agents can be developed that bind to different sites on amyloid deposits. In fact, in vivo cross-referencing studies based upon different amyloid-imaging agents may permit better characterization of AD pathology. But more importantly, novel amyloid imaging agents are required that will allow direct correlation between the results of animal models and human subjects based upon identical imaging modalities. Thus far, amyloid stains such as Congo red and thioflavin T have been extensively studied. However, another widely used amyloid dye, thioflavin S, has not been previously explored. This is in part due to the fact that thioflavin S exists as a mixture, not a pure chemical entity, albeit that the major component has been characterized. We hypothesized that neutral analogs, based upon the major component, could be developed as novel amyloid imaging agents, that exhibit complementary binding properties and pharmacokinetic profiles compatible with potential human studies.
KW - Alzheimer's disease
KW - Amyloid
KW - Congo red
KW - Thioflavin S
KW - Thioflavin T
UR - http://www.scopus.com/inward/record.url?scp=20844451743&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20844451743&partnerID=8YFLogxK
U2 - 10.2174/1567205053585864
DO - 10.2174/1567205053585864
M3 - Article
C2 - 15974905
AN - SCOPUS:20844451743
SN - 1567-2050
VL - 2
SP - 109
EP - 114
JO - Current Alzheimer Research
JF - Current Alzheimer Research
IS - 2
ER -