2-Phenylbenzothiazole conjugated with cyclopentadienyl tricarbonyl [CpM(CO)3] (M = Re, (99m)Tc) complexes as potential imaging probes for β-amyloid plaques.
Technetium-99m-labeled cyclopentadienyl tricarbonyl complexes conjugated with the 2-phenylbenzothiazole binding motif were synthesized. The rhenium surrogates , , and were demonstrated to have moderate to high affinities for Aβ1-42 aggregates with Ki values of 142, 76, 64 and 24 nM, respectively. During the fluorescence staining of brain sections of transgenic mice and patients with Alzheimer's disease, these rhenium complexes demonstrated perfect and intense labeling of Aβ plaques. Moreover, in in vitro autoradiography, (99m)Tc-labeled complexes clearly detected β-amyloid plaques on sections of brain tissue from transgenic mice, which confirmed the sufficient affinity of these tracers for Aβ plaques. However, these compounds did not show desirable properties in vivo, especially showing poor brain uptake (below 0.5% ID g(-1)), which will hinder the further development of these tracers as brain imaging agents. Nonetheless, it is encouraging that these (99m)Tc-labeled complexes designed by a conjugate approach displayed sufficient affinities for Aβ plaques.
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China. cmc@bnu.edu.cn.
Jianhua
J
Jia
Mengchao
M
Cui
Jiapei
J
Dai
Boli
B
Liu
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D056831:Coordination Complexes / Q000737:chemistry*; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D066263:Protein Aggregation, Pathological; D012211:Rhenium / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D056831:Coordination Complexes; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D012211:Rhenium; D013667:Technetium; C070845:2-phenylbenzothiazole