Development of a ²¹³Bi-Labeled Pyridyl Benzofuran for Targeted α-Therapy of Amyloid-β Aggregates

Previously reported amyloid imaging agents and derivative labeled with ²¹¹At, as method of TAT for AD. RCY = radiochemical yield.

(A) Retrosynthetic analysis of TAT reagent for AD. (B) ²¹³Bi decay chain.

Synthesis of fluorescent BPy and 8.

(A) Ultraviolet–visible spectroscopy (UV-Vis) and ²¹³Bi counts of BiBPy. (B) Specific activity of 8: 120.6 GBq/μg BiBPy. (C) Binding competition assay against thioflavin-S; 8 dissociation constant (K_D) is 11 ± 1.5 nM. (D) Comparison of 8 K_D to other small-molecule agents for amyloid plaques.

(A) Amyloid-β (Aβ) plaque reduction, measured by enzyme-linked immunosorbent assay, as function of increasing ²¹³Bi activity, free or targeted. (B) Fitting of amyloid-β reduction as function of activity. (C) Western blot analysis of amyloid-β after exposure to [²¹³Bi]BiBPy confirms enzyme-linked immunosorbent assay trend of reduced plaque concentration. (D) When targeting of 8 is not blocked, plaque concentration is markedly less than when targeting is blocked (here, by 1). GAPDH = glyceraldehyde 3-phosphate dehydrogenase.