A highly selective and specific PET tracer for imaging of tau pathologies.
Senile plaques and neurofibrillary tangles are prominent neuropathological hallmarks in Alzheimer's disease and are considered to be targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. While there are a number of amyloid-β positron emission tomography (PET) tracers currently in different stages of clinical development and commercialization, there have been very few reports on imaging agents selectively targeting tau aggregates. In search of [18F]-PET tracers that possess great binding affinity and selectivity toward tau tangles, we tested more than 900 compounds utilizing a unique screening process. A competitive autoradiography assay was set up to test compounds for binding to native tau tangles and amyloid-β plaques on human brain tissue sections. In our in vitro assays, the 18F labeled compound [18F]-T808 displayed a high level of binding affinity and good selectivity for tau aggregates over amyloid-β plaques. [18F]-T808 showed rapid uptake and washout in rodent brains. Our in vitro and preclinical in vivo studies suggest that [18F]-T808 possesses suitable properties and characteristics to be a specific and selective PET probe for imaging of paired helical filament tau in human brains.
Siemens Molecular Imaging, Inc., Culver City, CA 90230, USA.
Wei
W
Zhang
Janna
J
Arteaga
Daniel K
DK
Cashion
Gang
G
Chen
Umesh
U
Gangadharmath
Luis F
LF
Gomez
Dhanalakshmi
D
Kasi
Chung
C
Lam
Qianwa
Q
Liang
Changhui
C
Liu
Vani P
VP
Mocharla
Fanrong
F
Mu
Anjana
A
Sinha
A Katrin
AK
Szardenings
Eric
E
Wang
Joseph C
JC
Walsh
Chunfang
C
Xia
Chul
C
Yu
Tieming
T
Zhao
Hartmuth C
HC
Kolb
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001345:Autoradiography / Q000379:methods; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D005462:Fluorine Radioisotopes; C054369:MAPT protein, human; D019275:Radiopharmaceuticals; D016875:tau Proteins