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Fluselenamyl: A Novel Benzoselenazole Derivative for PET Detection of Amyloid Plaques (A?) in Alzheimer's Disease.


ABSTRACT: Fluselenamyl (5), a novel planar benzoselenazole shows traits desirable of enabling noninvasive imaging of A? pathophysiology in vivo; labeling of both diffuse (an earlier manifestation of neuritic plaques) and fibrillar plaques in Alzheimer's disease (AD) brain sections, and remarkable specificity for mapping A? compared with biomarker proteins of other neurodegenerative diseases. Employing AD homogenates, [18F]-9, a PET tracer demonstrates superior (2-10 fold higher) binding affinity than approved FDA tracers, while also indicating binding to high affinity site on A? plaques. Pharmacokinetic studies indicate high initial influx of [18F]-9 in normal mice brains accompanied by rapid clearance in the absence of targeted plaques. Following incubation in human serum, [18F]-9 indicates presence of parental compound up to 3h thus indicating its stability. Furthermore, in vitro autoradiography studies of [18F]-9 with AD brain tissue sections and ex vivo autoradiography studies in transgenic mouse brain sections show cortical A? binding, and a fair correlation with A? immunostaining. Finally, multiphoton- and microPET/CT imaging indicate its ability to penetrate brain and label parenchymal plaques in transgenic mice. Following further validation of its performance in other AD rodent models and nonhuman primates, Fluselenamyl could offer a platform technology for monitoring earliest stages of A? pathophysiology in vivo.

SUBMITTER: Sundaram GS 

PROVIDER: S-EPMC5090206 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Fluselenamyl: A Novel Benzoselenazole Derivative for PET Detection of Amyloid Plaques (Aβ) in Alzheimer's Disease.

Sundaram G S M GS   Dhavale Dhruva D DD   Prior Julie L JL   Yan Ping P   Cirrito John J   Rath Nigam P NP   Laforest Richard R   Cairns Nigel J NJ   Lee Jin-Moo JM   Kotzbauer Paul T PT   Sharma Vijay V  

Scientific reports 20161102


Fluselenamyl (5), a novel planar benzoselenazole shows traits desirable of enabling noninvasive imaging of Aβ pathophysiology in vivo; labeling of both diffuse (an earlier manifestation of neuritic plaques) and fibrillar plaques in Alzheimer's disease (AD) brain sections, and remarkable specificity for mapping Aβ compared with biomarker proteins of other neurodegenerative diseases. Employing AD homogenates, [<sup>18</sup>F]-9, a PET tracer demonstrates superior (2-10 fold higher) binding affinit  ...[more]

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