[(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease.
Alzheimers Dement
; 9(6): 666-76, 2013 Nov.
Article
in En
| MEDLINE
| ID: mdl-23411393
ABSTRACT
OBJECTIVE:
We wished to develop a highly selective positron emission tomography (PET) imaging agent targeting PHF-tau in human Alzheimer's disease (AD) brains.METHODS:
To screen potential tau binders, human AD brain sections were used as a source of native paired helical filament (PHF)-tau and Aß rather than synthetic tau aggregates or Aß fibrils generated in vitro to measure the affinity and selectivity of [(18)F]T807 to tau and Aß. Brain uptake and biodistribution of [(18)F]T807 in mice were also tested.RESULTS:
In vitro autoradiography results show that [(18)F]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant (Kd) of [(18)F]T807 (14.6 nM) was measured using brain sections from the frontal lobe of AD patients. A comparison of autoradiography and double immunohistochemical staining of PHF-tau and Aß on adjacent sections demonstrated that [(18)F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Aß plaques. In vivo studies in mice demonstrated that [(18)F]T807 was able to cross the blood-brain barrier and washed out quickly.CONCLUSIONS:
[(18)F]T807 demonstrates high affinity and selectivity to PHF-tau as well as favorable in vivo properties, making this a promising candidate as an imaging agent for AD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Fluorine Radioisotopes
/
Tau Proteins
/
Alzheimer Disease
Type of study:
Observational_studies
Limits:
Aged
/
Aged80
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Alzheimers Dement
Year:
2013
Document type:
Article
Affiliation country:
Estados Unidos