Novel Cyclopentadienyl Tricarbonyl Complexes of ^99mTc Mimicking Chalcone as Potential Single-Photon Emission Computed Tomography Imaging Probes for β-Amyloid Plaques in Brain

Abstract

Rhenium and technetium-99m cyclopentadienyl tricarbonyl complexes mimicking the chalcone structure were prepared. These complexes were proved to have affinity to β-amyloid (Aβ) in fluorescent staining on brain sections of Alzheimer's Disease (AD) patient and binding assay using Aβ(1-42) aggregates, with K(i) values ranging from 899 to 108 nM as the extension of conjugated π system. In vitro autoradiograpy on sections of transgenic mouse brain confirmed the affinity of [(99m)Tc]5 (K(i) = 108 nM). In biodistribution, all compounds showed good initial uptakes into the brain and fast blood clearance, while the decreasing of initial brain uptakes correspond to increasing of conjugation length, from 4.10 ± 0.38% ID/g ([(99m)Tc]3) to 1.11 ± 0.34% ID/g ([(99m)Tc]5). These small technetium-99m complexes (<500 Da) designed by an integrated approach provide encouraging evidence that development of a promising (99m)Tc-labeled agent for imaging Aβ plaques in the brain may be feasible.

Synthesis, Characterization, and Antibacterial Activities of Some New Zinc Coordination Compounds of an Asymmetric Bidentate Schiff Base

“…Comparison between IR spectra of primary amine and aldehyde with the ligand represents that some characteristic wave numbers of parental aldehyde and amine are eliminated and instead of them, a new strong wave number at 1599 cm ¡1 is appeared, which was assigned to the formation of the iminic CHN groups. [28,34,35] After coordination, vibration of iminic bound were shifted to lower wave numbers 1583-1588 cm ¡1 (e.g., up to 16 cm ¡1 ) and therefore coordination of ligand to zinc ion via iminic nitrogens is confirmed perfectly. This lowering of vibrational frequency is due to (a) coordination of azomethine nitrogen inducing positive formal charge on nitrogen that lead to decrease of bonding electron density of imine bond and (b) p-back bonding from metal to iminic anti-bonding orbital leading to less bond order of imine bond that causes vibration of imine bound at lower wave numbers.…”

Synthesis and evaluation of ethyleneoxylated and allyloxylated chalcone derivatives for imaging of amyloid β plaques by SPECT

“…Indeed, it was reported that several Aβ probes with single-digit nanomolar Ki values for the Aβ aggregates successfully stained the Aβ plaques in brain sections of the Tg2576 mice by in vitro autoradiography 25,26 . In addition, it has been shown that chalcone derivatives with a dimethylamino group at the third position can be used to visualize Aβ plaques by in vitro autoradiography 19,27 . Thus, chalcone derivatives with a dimethylamino group in the 3-phenyl ring may be more suitable than those with an alkoxy group with respect to binding of the Aβ plaques in the brain.…”

“…Considerable effort has been devoted to the development of SPECT probes labeled with 99m Tc or 123/125 I for the Aβ plaques [8][9][10][11][12][13] . However, none of them have been approved by the Food and Drugs Administration (FDA) and/or the European Medicines Agency (EMA).…”

Radiopharmaceuticals in China: current status and prospects

“…Therefore, the development of novel imaging agents specifically targeting A plaques may lead to early diagnosis of AD and monitoring of the effectiveness of novel therapies for this devastating disease. [10], 99m Tc-labeled benzothiazole [11,12], phenylbenzoxazole derivatives [13], 6-dialkylamino-2-naphthylethylidene derivatives [14], dibenzylideneacetone derivatives [15], and cyclopentadienyl tricarbonyl complexes mimicking chalcone [16], 125 I-labeled anilinophthalimide [17], N-benzoylindole [18], ( )-5-styryl-2,2 -bithiophene derivatives [19], ( )-5-styryl-1 -indole and ( )-6-styrylquinoline derivatives [20] have been reported in the past decade. Among them,…”