A Phenylbenzothiazole Conjugate with the Tricarbonyl fac-[M(I)(CO)3]+ (M=Re, 99Tc, 99mTc) Core for Imaging of β-Amyloid Plaques

The 2-(4'-aminophenyl)-6-methylbenzothiazole that is known to display affinity and specificity toward the amyloid plaques of Alzheimer's disease (AD) has been joined to the tricarbonyl [M(CO)3NNO] chelate (M = Re, 99Tc, and 99mTc) through a five-carbon linker chain to generate the neutral complex 1 (namely, Re-1 for M = Re; 99Tc-1 for M = 99Tc; and 99mTc-1 for M = 99mTc) with the aim of developing a single-photon emission computed tomography (SPECT) radiodiagnostic agent for AD. Re-1 was characterized by spectroscopic methods and X-ray crystallography, whereas the detailed NMR spectroscopic analysis of 99Tc-1 demonstrated its structural similarity to Re-1. Complexes Re-1 and 99Tc-1 display selective binding affinity for amyloid plaques as evidenced by fluorescence spectroscopy, whereas the biodistribution data of 99mTc-1?characterized by relatively low brain uptake, fast clearance from brain and blood, and in vivo stability?are considered encouraging for further elaboration on the structural features of 1 in the direction of increased brain uptake.