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

作者：Watanabe Hiroyuki; Ono Masahiro^*; Iikuni Shimpei; Yoshimura Masashi; Matsumura Kenji; Kimura Hiroyuki; Saji Hideo

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(20): 4834-4837.

DOI：10.1016/j.bmcl.2014.08.058

• Amyloid
• imaging
• PET
• Probe
• Ga-68

Since the imaging of beta-amyloid (A beta) 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 A13 plaques have been developed. Because the radionuclide Ga-68 (t(1/2)= 68 min) for PET imaging could become an attractive alternative to C-11 and F-18, we designed and synthesized a benzofuran derivative conjugated with a Ga-68 complex (68Ga-DOTA-C3-BF) as a novel A13 imaging probe. In an in vitro binding assay, Ga-DOTA-C3-BF showed high affinity for A beta(1-42) aggregates (K-i = 10.8 nM). The Ga-DOTA-C3-BF clearly stained A beta plaques in a section of Tg2576 mouse, reflecting the affinity for A13(1-42) aggregates in vitro. In a biodistribution study in normal mice, Ga-68-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 Ga-68 complexes appears to be essential, these results suggest that novel PET imaging probes that include Ga-68 as the radionuclide for PET may be feasible.

• 出版日期2014-10-15