The latest entry in the roster of tau imaging agents is a 11
C tracer: 11
C-PBB3, based on a phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs) scaffold. These compounds are characterized by a π-electron-conjugated backbone with a specific extent ranging from 13 to19 Å that apparently allows binding to a broad range of AD and non-AD tau aggregates. Several PBB candidates underwent a thorough preclinical evaluation. While in-vitro autoradiographic studies in AD brain sections showed substantial non-selective binding, two-photon laser scanning fluorescence microscopy studies in a tau transgenic mouse model showed rapid clearance of the tracer with selective binding to tau tangles. Similar results were observed in microPET studies, showing higher PBB3 binding in the spinal cord of the same transgenic tau mouse model.
Preliminary clinical studies in three healthy control volunteers and three AD patients assessed with both 11C-PBB3 and 11C-PiB showed a different pattern of brain retention between the two tracers,...
The sensitivity and specificity of tau tracers for human tau pathology cannot be known until there have been a substantial number of imaged patients with autopsies and neuropathological diagnoses. Clinical diagnostic accuracy for non-Alzheimer's dementias, including corticobasal degeneration is poor (see references) and cannot be a substitute for autopsy. It will be difficult to devise tau ligands that do not also bind to Aβ; amyloid and it will take autopsy to prove this.
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