Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes

In continuation of the investigation on the bithiophene structure as potential Aβ probes, two halogenated chalcone derivatives containing bithiophene moiety were designed and evaluated as imaging probes for Aβ plaques. In vitro fluorescence staining indicated that they could stain Aβ plaques in the...

Full description

Bibliographic Details
Main Authors: PENG Cheng, CUI Meng-chao, LIANG Zhi-gang, LIU Ting-ting
Format: Article
Language:zho
Published: Editorial Board of Journal of Isotopes 2015-11-01
Series:Journal of Isotopes
Subjects:
Online Access:http://www.tws.org.cn/CN/10.7538/tws.2015.28.04.0253
id doaj-e4a4c8f4461d4d22853300266a3dcb75
record_format Article
spelling doaj-e4a4c8f4461d4d22853300266a3dcb752020-11-25T02:22:17ZzhoEditorial Board of Journal of IsotopesJournal of Isotopes1000-75121000-75122015-11-0128425325810.7538/tws.2015.28.04.0253 Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ ProbesPENG Cheng0CUI Meng-chao1LIANG Zhi-gang2LIU Ting-ting3Xuanwu Hospital,Capital Medical UniversityKey Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education,College of ChemistryXuanwu Hospital,Capital Medical UniversityXuanwu Hospital,Capital Medical UniversityIn continuation of the investigation on the bithiophene structure as potential Aβ probes, two halogenated chalcone derivatives containing bithiophene moiety were designed and evaluated as imaging probes for Aβ plaques. In vitro fluorescence staining indicated that they could stain Aβ plaques in the brain sections of AD model mice specifically, in vitro binding assay further confirmed that they displayed high binding affinities to Aβ aggregates (Ki=2.33 nM and 0.88 nM). One radio-iodinated probe, 125I labeleled chalcone derivatives was obtained via iododestannylation reaction with high radiochemical yield and purity (>99%). Moreover, the 125I-labeling compound displayed specific labeling of Aβ plaques in the brain sections of AD model mice with low background, and the specific labeling could be confirmed by thioflavin-S staining. In vivo biodistribution in normal mice indicated that the 125I labeling compound exhibited low initial brain uptake (1.19%ID/g at 2 min) and rapid clearance. These preliminary results suggest that 125I labeling compound may serve as novel Aβ imaging probe, although further modifications are needed to improve initial brain uptake. http://www.tws.org.cn/CN/10.7538/tws.2015.28.04.0253 Alzheimer’s diseaseA&betaplaquesautoradiographybiodistribution
collection DOAJ
language zho
format Article
sources DOAJ
author PENG Cheng
CUI Meng-chao
LIANG Zhi-gang
LIU Ting-ting
spellingShingle PENG Cheng
CUI Meng-chao
LIANG Zhi-gang
LIU Ting-ting
Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes
Journal of Isotopes
Alzheimer’s disease
A&beta
plaques
autoradiography
biodistribution
author_facet PENG Cheng
CUI Meng-chao
LIANG Zhi-gang
LIU Ting-ting
author_sort PENG Cheng
title Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes
title_short Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes
title_full Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes
title_fullStr Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes
title_full_unstemmed Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes
title_sort synthesis and evaluation of 125i labeled chalcone derivatives containing bithiophene moiety as potential aβ probes
publisher Editorial Board of Journal of Isotopes
series Journal of Isotopes
issn 1000-7512
1000-7512
publishDate 2015-11-01
description In continuation of the investigation on the bithiophene structure as potential Aβ probes, two halogenated chalcone derivatives containing bithiophene moiety were designed and evaluated as imaging probes for Aβ plaques. In vitro fluorescence staining indicated that they could stain Aβ plaques in the brain sections of AD model mice specifically, in vitro binding assay further confirmed that they displayed high binding affinities to Aβ aggregates (Ki=2.33 nM and 0.88 nM). One radio-iodinated probe, 125I labeleled chalcone derivatives was obtained via iododestannylation reaction with high radiochemical yield and purity (>99%). Moreover, the 125I-labeling compound displayed specific labeling of Aβ plaques in the brain sections of AD model mice with low background, and the specific labeling could be confirmed by thioflavin-S staining. In vivo biodistribution in normal mice indicated that the 125I labeling compound exhibited low initial brain uptake (1.19%ID/g at 2 min) and rapid clearance. These preliminary results suggest that 125I labeling compound may serve as novel Aβ imaging probe, although further modifications are needed to improve initial brain uptake.
topic Alzheimer’s disease
A&beta
plaques
autoradiography
biodistribution
url http://www.tws.org.cn/CN/10.7538/tws.2015.28.04.0253
work_keys_str_mv AT pengcheng synthesisandevaluationof125ilabeledchalconederivativescontainingbithiophenemoietyaspotentialabprobes
AT cuimengchao synthesisandevaluationof125ilabeledchalconederivativescontainingbithiophenemoietyaspotentialabprobes
AT liangzhigang synthesisandevaluationof125ilabeledchalconederivativescontainingbithiophenemoietyaspotentialabprobes
AT liutingting synthesisandevaluationof125ilabeledchalconederivativescontainingbithiophenemoietyaspotentialabprobes
_version_ 1724862279863762944