Monoamine oxidase binding not expected to significantly affect [¹⁸F]flortaucipir PET interpretation

Area of Science:

• Neuroimaging
• Radiochemistry
• Biochemistry

Background:

• Positron emission tomography (PET) radioligands like [18F]flortaucipir are crucial for assessing Alzheimer's disease biomarkers in vivo.
• Neurofibrillary tau (NFT) pathology is a key target for PET imaging, with [18F]flortaucipir showing promise.

Purpose of the Study:

• To investigate the potential binding of [18F]flortaucipir to monoamine oxidase A (MAO-A) and MAO-B.
• To determine if MAO-A or MAO-B binding could impact the interpretation of [18F]flortaucipir PET scans.

Main Methods:

• Autoradiography on human brain tissue and in vivo PET imaging in rats were employed.
• Saturation, kinetic, and competition binding experiments were conducted to quantify binding affinities and rates.

Main Results:

• Specific [18F]flortaucipir binding was confirmed in tau NFT-rich Alzheimer's disease tissue.
• [18F]Flortaucipir showed no significant in vivo binding to MAO-A in rats, and in vitro studies indicated rapid dissociation from MAO-A.
• Weak in vitro binding to MAO-B was observed only at high micromolar concentrations, insufficient to affect PET interpretation.

Conclusions:

• Binding to MAO-A and MAO-B does not significantly contribute to the PET signal in cortical regions relevant for [18F]flortaucipir interpretation.
• The findings support the use of [18F]flortaucipir for accurate assessment of neurofibrillary tau pathology in Alzheimer's disease.