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Employing in vitro metabolism to guide design of F-labelled PET probes of novel alpha-synuclein binding bifunctional compounds

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dc.contributor.authorNwabufo, Chukwunonso
dc.contributor.authorAigbogun, Omozojie
dc.contributor.authorAllen, Kevin
dc.contributor.authorMadeline N. Owens
dc.contributor.authorJeremy S. Lee
dc.contributor.authorChristopher P. Phenix
dc.contributor.authorKrol, Ed
dc.date.accessioned2021-10-27T20:09:11Z
dc.date.available2021-10-27T20:09:11Z
dc.date.issued2021-06-30
dc.description.abstract1. A challenge in the development of novel 18F-labelled positron emission tomography (PET) imaging probes is identification of metabolically stable sites to incorporate the 18F radioisotope. Metabolic loss of 18F from PET probes in vivo can lead to misleading biodistribution data as displaced 18F can accumulate in various tissues. 2. In this study we report on in vitro hepatic microsomal metabolism of novel caffeine containing bifunctional compounds (C8-6-I, C8-6-N, C8-6-C8) that can prevent in vitro aggregation of -synuclein, which is associated with the pathophysiology of Parkinson’s disease. The metabolic profile obtained guided us to synthesize stable isotope 19F-labelled analogues in which the fluorine was introduced at the metabolically stable N7 of the caffeine moiety. 3. An in vitro hepatic microsomal metabolism study of the 19F-labelled analogues resulted in similar metabolites to the unlabelled compounds and demonstrated that the fluorine was metabolically stable, suggesting that these analogues are appropriate PET imaging probes. This straightforward in vitro strategy is valuable for avoiding costly stability failures when designing radiolabelled compounds for PET imaging.en_US
dc.description.sponsorshipNSERCen_US
dc.description.versionPeer Revieweden_US
dc.identifier.citationChukwunonso K. Nwabufo, Omozojie P. Aigbogun, Kevin J.H Allen, Madeline N. Owens, Jeremy S. Lee, Christopher P. Phenix & Ed S. Krol (2021). Employing in vitro metabolism to guide design of F-labelled PET probes of novel α-synuclein binding bifunctional compounds, Xenobiotica, 51:8, 885-900. 10.1080/00498254.2021.1943566en_US
dc.identifier.doi10.1080/00498254.2021.1943566
dc.identifier.urihttps://hdl.handle.net/10388/13661
dc.language.isoenen_US
dc.publisherTaylor & Francisen_US
dc.rightsAttribution 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/ca/*
dc.subjectMicrosomal metabolismen_US
dc.subjectPositron Emission Tomographyen_US
dc.subjectImaging probe designen_US
dc.subjectalpha-synucleinen_US
dc.subjectParkinson’s diseaseen_US
dc.subjectFluorine radiolabellingen_US
dc.titleEmploying in vitro metabolism to guide design of F-labelled PET probes of novel alpha-synuclein binding bifunctional compoundsen_US
dc.typePostprinten_US

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