第二世代タウPETトレーサーの結合性比較

<p>Introduction: Misfolded tau aggregates associated with clinical syndromes and various neurodegenerative diseases. To date, many second-generation of tau PET tracers were developed to overcome the limitation of the first-generation such as off-target binding. Recently, we developed [¹⁸F]SNFT-1 from compound optimization of [¹⁸F]THK-5351, which showed high affinity for monoamine oxidase-B (MAO-B) as off-target binding. The aim of study was to compare the binding properties of [¹⁸F]SNFT-1 and second-generation tau PET radiotracers to human brain tissues.</p><p>Methods: In vitro competitive binding assay were performed for tau aggregates, amyloid aggregates, and recombinant MAO-A and MAO-B. After preparing ¹⁸F-labeled compounds, in vitro autoradiography was performed using frozen human brain sections with immunostaining of phosphorylated tau (tau IHC) for evaluation of binding selectivity.</p><p>Results and Discussion: Although second-generation of tau PET radiotracers showed a similar binding affinity for tau aggregates, the off-target binding affinity was different. SNFT-1 showed a high binding affinity for tau aggregates, which was comparable to MK-6240, with no interaction of amyloid aggregates as well as MAO enzymes. In vitro autoradiography demonstrated that distribution of radiotracer&apos;s binding was similar to tau IHC in the medial temporal area of Alzheimer&apos;s disease. On the other hands, second-generation tau PET radiotracers showed little binding to the frontal cortex in a case of progressive supranuclear palsy that contains high density tau aggregates. </p><p>Conclusion: [¹⁸F]SNFT-1 would be a promising candidates for imaging tau aggregates. Further binding characterization is required to validate the binding of non-AD tau aggregates.</p>