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

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 <i>fac</i>-[M­(CO)₃]⁺ (M = Re­(I), ^99mTc­(I)) core through the cyclopentadienyl moiety to yield stable, neutral, and lipophilic complexes (<b>Re-1</b> and ^<b>99m</b><b>Tc-1</b>, respectively). The <b>Re-1</b> complex was completely characterized with spectroscopic methods and was shown to selectively stain Aβ plaques on sections of human AD brain tissue. The ^<b>99m</b><b>Tc-1</b> complex displayed satisfactory initial brain uptake (0.53% ID/g at 2 min) and <i>in vivo</i> 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

Synthesis and Characterization of <i>fac</i>-[M(CO)₃(P)(OO)] and <i>cis-trans</i>-[M(CO)₂(P)₂(OO)] Complexes (M = Re, ^99mTc) with Acetylacetone and Curcumin as OO Donor Bidentate Ligands

The synthesis and characterization of neutral mixed ligand complexes <i>fac-</i>[M­(CO)₃(P)­(OO)] and <i>cis-trans</i>-[M­(CO)₂(P)₂(OO)] (M = Re, ^99mTc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding <i>fac-</i>[M­(CO)₃(H₂O)­(OO)] (M = Re, ^99mTc) intermediate aqua complex. In the presence of phosphine, replacement of the H₂O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine <i>fac</i>-[Re­(CO)₃(P)­(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex <i>cis-trans</i>-[Re­(CO)₂(P)₂(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimer’s disease. At the ^99mTc tracer level, the same type of complexes, <i>fac</i>-[^99mTc­(CO)₃(P)­(OO)] and <i>cis-trans</i>-[^99mTc­(CO)₂(P)₂(OO)], are formed introducing new donor combinations for ^99mTc­(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re­(I) and ^99mTc­(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system

Synthesis and Characterization of <i>fac</i>-[M(CO)₃(P)(OO)] and <i>cis-trans</i>-[M(CO)₂(P)₂(OO)] Complexes (M = Re, ^99mTc) with Acetylacetone and Curcumin as OO Donor Bidentate Ligands

The synthesis and characterization of neutral mixed ligand complexes <i>fac-</i>[M­(CO)₃(P)­(OO)] and <i>cis-trans</i>-[M­(CO)₂(P)₂(OO)] (M = Re, ^99mTc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding <i>fac-</i>[M­(CO)₃(H₂O)­(OO)] (M = Re, ^99mTc) intermediate aqua complex. In the presence of phosphine, replacement of the H₂O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine <i>fac</i>-[Re­(CO)₃(P)­(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex <i>cis-trans</i>-[Re­(CO)₂(P)₂(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimer’s disease. At the ^99mTc tracer level, the same type of complexes, <i>fac</i>-[^99mTc­(CO)₃(P)­(OO)] and <i>cis-trans</i>-[^99mTc­(CO)₂(P)₂(OO)], are formed introducing new donor combinations for ^99mTc­(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re­(I) and ^99mTc­(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system