2-Arylbenzothiazoles labeled with [CpRe/ 99m Tc(CO) 3 ] and evaluated as β-amyloid imaging probes.

An array of complexes, 99mTc/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/99mTc(CO)3] 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 Aβ1-42 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 [99mTc]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 99mTc-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.