A 68Ga complex based on benzofuran scaffold for the detection of β-amyloid plaques

Since the imaging of β-amyloid (Aβ) plaques in the brain is believed to be a useful tool for the early diagnosis of Alzheimer’s disease (AD), a number of imaging probes to detect Aβ plaques have been developed. Because the radionuclide 68Ga (t1/2 = 68 min) for PET imaging could become an attractive alternative to 11C and 18F, we designed and synthesized a benzofuran derivative conjugated with a 68Ga complex (68Ga-DOTA-C3-BF) as a novel Aβ imaging probe. In an in vitro binding assay, Ga-DOTA-C3-BF showed high affinity for Aβ(1-42) aggregates (Ki = 10.8 nM). The Ga-DOTA-C3-BF clearly stained Aβ plaques in a section of Tg2576 mouse, reflecting the affinity for Aβ(1-42) aggregates in vitro. In a biodistribution study in normal mice, 68Ga-DOTA-C3-BF displayed low initial uptake (0.45% ID/g) in the brain at 2 min post-injection. While improvement of the brain uptake of 68Ga complexes appears to be essential, these results suggest that novel PET imaging probes that include 68Ga as the radionuclide for PET may be feasible.

Graphical abstractThis Letter describes a 68Ga complex based on benzofuran scaffold for the detection of β-amyloid plaques.Figure optionsDownload full-size imageDownload as PowerPoint slide