A new PET radiotracer for tau pathologies is showing promise for helping diagnose and differentiate Alzheimer's disease (AD) from a wide range of other dementia disorders. Researchers detailed their early experiences in animal and patient studies in Neuron online October 29.

The PET radiopharmaceutical -- F-18 PM-PBB3 -- was developed in Japan at the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology. It is being tested in clinical trials under the name of APN-1607 through a tie-up with Taiwan start-up Aprinoia Therapeutics.

In the Neuron report, a team led by Dr. Makoto Higuchi, PhD, of the National Institutes for Quantum and Radiological Science and Technology explained how the radiotracer works, outlined its advantages over other PET tracers for tau pathologies, and described experience in 39 patients with Alzheimer's disease, as well as a range of frontal-temporal lobar degeneration (FTLD) conditions, notably the following:

• Pick's disease
• Progressive supranuclear palsy
• Corticobasal degeneration

Tau pathology occurs in diverse illnesses and is mechanistically linked to the neurodegenerative processes of these disorders, the authors noted in Neuron. The manner in which abnormal tau proteins build up typically differs for Alzheimer's disease and Alzheimer's type primary age-related tauopathy compared with FTLD disorders..

The study shows how the location of abnormal tau protein aggregates in parts of the brain signaled which particular condition patients had, results that were confirmed on biopsies and autopsies.

The imaging probe C-11 PBB3 has been positioned for use for imaging tau pathologies, but a major limitation of this tracer is that it rapidly converts to a metabolite, resulting in low entry of the unmetabolized compound into the brain, "hampering a sensitive recognition of fibrillary aggregates in FTLD tauopathies that are less abundant than AD tau deposits" the authors wrote.

"To overcome this technical issue, in the current work, we modified the chemical structure of PBB3 to generate a chemical with a relatively high metabolic stability, aiming at unambiguous investigations of tau fibril density and extent in each of the individuals with AD and FTLD," the authors explained.

The new compound was fluorinated because an F-18 labeled probe has broader availability and higher PET scan throughput compared with C-11 radiochemicals, the authors noted.

Uptake in the brain with F-18 PM-PBB3 was shown to be approximately twice as high as for C-11 PBC, according to the study. The authors also reported that PET images show the stability of the new probe in patients with dementia in contrast with low retention in healthy controls.

"The clearance of [F-18 PM-PBB3] was profoundly slowed in tau-burdened areas of the AD and [progressive supranuclear palsy] brains, conceivably reflecting the specific radioligand binding to tau aggregates," Higuchi et al wrote.

Based on PM-PBB3-positive tau deposits, it's possible to make clear separations between disorders, which has not been possible with other tau PET probes and other imaging modalities, such as volumetric MRI, the authors wrote. This "paves the way for the construction of a biomonitoring system for the selection of an adequate disease-modifying therapeutic," according to Higuchi et al.

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