Objective <p>Amyloid-β (Aβ) aggregates have been recognized as therapeutic targets for Alzheimer’s disease (AD). Targeted alpha therapy (TAT) using α-particles has the potential to be applied as a novel treatment approach for AD by reducing the quantity of Aβ aggregates. In this study, we developed a novel astatine-211-labeled pyridyl benzofuran (PBF) derivative, [²¹¹At]APBF-2, as a small molecule-based Aβ-TAT agent and evaluated its potential for in vivo use.</p> Methods <p>[²¹¹At]APBF-2 was synthesized in a one-step astatination process using the tributyltin precursor. In the Aβ aggregation inhibition assay, [²¹¹At]APBF-2 was added to a sample containing Aβ_1–42 monomers and thioflavin-T (ThT) and the mixture was incubated for 24&#xa0;h. The quantity of Aβ aggregates was evaluated by measuring ThT fluorescence intensity. The biodistribution of [²¹¹At]APBF-2 (25&#xa0;kBq/100 μL) was evaluated using ddY mice (<i>n</i> = 5).</p> Results <p>[²¹¹At]APBF-2 was synthesized in radiochemical yield of 57% with a radiochemical purity of over 95%. In the in vitro assay, [²¹¹At]APBF-2 showed a dose-dependent decrease in ThT fluorescence intensity, suggesting the ability of [²¹¹At]APBF-2 to inhibit Aβ aggregation. In the biodistribution study using normal mice, the initial brain uptake of [²¹¹At]APBF-2 was observed (2.95% injected dose/g at 2&#xa0;min), demonstrating favorable&#xa0;Blood–brain barrier permeability.</p> Conclusions <p>These results suggest the feasibility of using [²¹¹At]APBF-2 as an Aβ-TAT agent for in vivo applications.</p>