Novel tau imaging agent takes dementia imaging to the next level

A tau-imaging agent has moved ahead of the pack to pick up strong signals of tau aggregates in the brain in patterns consistent with Alzheimer’s disease (AD), according a study published Sept. 18 in Neuron.

The revelation of tau fibril imaging is thought to be as important as visualizing beta amyloid deposition when evaluating patients for neurodegenerative disorders like AD.

Masahiro Maruyama, MD, from the Molecular Imaging Center at the National Institute of Radiological Sciences in Chiba, Japan, and colleagues performed imaging studies using both optical and PET scanning technology to evaluate investigational tracers for their ability to bind to intracellular tau inclusions. A new class of imaging agents—phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs)—showed exemplary binding when conjugated in this study with carbon-11.

AD imaging has been lacking a viable vehicle for visualizing tau pathology, a substantial piece of the puzzle for imaging AD and other neurodegenerative disorders. Amyvid, or F-18 florbetapir, a beta amyloid agent, is still currently the only FDA approved agent for dementia imaging, but it does not image tau fibrils in the brain. Still other potential tau agents have missed the mark.

“Thus, better tau radioligands with higher affinity for tau fibrils and/or less nonspecific binding to tissues are urgently needed to complement high-contrast senile plaque imaging agents, including widely studied C-11 Pittsburgh Compound-B (C-11 PIB) and United States Food and Drug Administration approved F-18 florbetapir,” wrote Maruyama et al. “In addition, F-18 FDDNP and several other candidate tau probes do not bind to tau inclusions in non-AD tauopathy brains without plaque deposition and therefore can be clinically characterized only in AD patients with comingled beta amyloid and tau amyloids. Hence, compounds that detect diverse tau aggregates, including tau inclusions in non-AD neurodegenerative diseases and tau Tg models, could be used to interrogate in vivo interactions between exogenous ligands and tau pathologies.”

For this study, researchers conducted both preclinical and clinical imaging, the latter with a compound of pyridinated C-11 PBB3, which showed “robust” signal in the hippocampus of the Alzheimer’s brain, and not only to represent tau fibrils, but a range of tau aggregation in line with the progression of AD and in clear contrast to C-11 PiB beta amyloid deposition.

C-11 PBB3 was also able to pick up corticobasal syndrome, which was not the case with C-11 PiB. Further studies are needed to validate the new tracer as a front-runner of next-generation dementia imaging agents.