2-(4′-Aminophenyl)benzothiazole Labeled with 99mTc-Cyclopentadienyl for Imaging β-Amyloid Plaques

Article abstract of DOI:10.1021/acsmedchemlett.7b00294

The development of a ^99mTc-radiotracer for imaging of β-amyloid (Aβ) plaques with single photon emission computed tomography (SPECT) is strongly anticipated to provide a low cost and broadly accessible diagnostic tool for Alzheimer's disease (AD). Within this framework, 2-(4′-aminophenyl)benzothiazole, known to display affinity and specificity for Aβ plaques, has been joined to the tricarbonyl fac-[M(CO)₃]⁺ (M = Re(I), ^99mTc(I)) core through the cyclopentadienyl moiety to yield stable, neutral, and lipophilic complexes (Re-1 and ^99mTc-1, respectively). The Re-1 complex was completely characterized with spectroscopic methods and was shown to selectively stain Aβ plaques on sections of human AD brain tissue. The ^99mTc-1 complex displayed satisfactory initial brain uptake (0.53% ID/g at 2 min) and in vivo stability in healthy mice, while in transgenic 5xFAD mice, models for AD, a notable retention in the brain was noted (1.94% ID/g at 90 min). The results are encouraging and contribute to the effort of developing a SPECT amyloid imaging agent.