2-Arylbenzothiazoles labeled with [CpRe/Tc(CO)] and evaluated as β-amyloid imaging probes.

An array of complexes, Tc/Re-labeled cyclopentadienyl tricarbonyl and 2-phenyl/pyridylbenzothiazoles, conjugated through an ester linkage were tested as potential β-amyloid (Aβ) probes for SPECT imaging. The [CpRe/Tc(CO)] complexes were prepared by double ligand transfer reactions from ferrocene precursors, and the X-ray structure of one rhenium surrogate revealed a classical "piano stool" like geometry. Several of the rhenium complexes displayed high affinity for Aβ aggregates in in vitro inhibition assays, and they could intensely stain Aβ deposits on brain sections from transgenic mice and Alzheimer's disease (AD) patients. Complex [Tc]4h strongly binds to Aβ deposits in blood vessels of the brain section of AD patients in in vitro autoradiography. Biodistribution experiments in normal mice revealed that Tc-labeled tracers exhibited moderate degree of initial brain uptake (0.54%-1.06% ID/g at 2 min). These tracers targeting Aβ plaques of AD patients warrant further structure optimization to improve their ability to penetrate blood-brain barrier, moreover, they may be suitable for developing imaging probes for targeting amyloid aggregates outside of the brain.