Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody

Abstract Brain positron emission tomography (PET) imaging with radiolabelled proteins is an emerging concept that potentially enables visualization of unique molecular targets in the brain. However, the pharmacokinetics and protein radiolabelling methods remain challenging. Here, we report the perfo...

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Autores principales:	Takahiro Morito, Ryuichi Harada, Ren Iwata, Yiqing Du, Nobuyuki Okamura, Yukitsuka Kudo, Kazuhiko Yanai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ed6b02705444b138a1da6dafa57c210
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spelling	oai:doaj.org-article:1ed6b02705444b138a1da6dafa57c2102021-12-02T10:48:31ZSynthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody10.1038/s41598-021-82037-22045-2322https://doaj.org/article/1ed6b02705444b138a1da6dafa57c2102021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82037-2https://doaj.org/toc/2045-2322Abstract Brain positron emission tomography (PET) imaging with radiolabelled proteins is an emerging concept that potentially enables visualization of unique molecular targets in the brain. However, the pharmacokinetics and protein radiolabelling methods remain challenging. Here, we report the performance of an engineered, blood–brain barrier (BBB)-permeable affibody molecule that exhibits rapid clearance from the brain, which was radiolabelled using a unique fluorine-18 labelling method, a cell-free protein radiosynthesis (CFPRS) system. AS69, a small (14 kDa) dimeric affibody molecule that binds to the monomeric and oligomeric states of α-synuclein, was newly designed for brain delivery with an apolipoprotein E (ApoE)-derived brain shuttle peptide as AS69-ApoE (22 kDa). The radiolabelled products 18F-AS69 and 18F-AS69-ApoE were successfully synthesised using the CFPRS system. Notably, 18F-AS69-ApoE showed higher BBB permeability than 18F-AS69 in an ex vivo study at 10 and 30 min post injection and was partially cleared from the brain at 120 min post injection. These results suggest that small, a brain shuttle peptide-fused fluorine-18 labelled protein binders can potentially be utilised for brain molecular imaging.Takahiro MoritoRyuichi HaradaRen IwataYiqing DuNobuyuki OkamuraYukitsuka KudoKazuhiko YanaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takahiro Morito Ryuichi Harada Ren Iwata Yiqing Du Nobuyuki Okamura Yukitsuka Kudo Kazuhiko Yanai Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody
description	Abstract Brain positron emission tomography (PET) imaging with radiolabelled proteins is an emerging concept that potentially enables visualization of unique molecular targets in the brain. However, the pharmacokinetics and protein radiolabelling methods remain challenging. Here, we report the performance of an engineered, blood–brain barrier (BBB)-permeable affibody molecule that exhibits rapid clearance from the brain, which was radiolabelled using a unique fluorine-18 labelling method, a cell-free protein radiosynthesis (CFPRS) system. AS69, a small (14 kDa) dimeric affibody molecule that binds to the monomeric and oligomeric states of α-synuclein, was newly designed for brain delivery with an apolipoprotein E (ApoE)-derived brain shuttle peptide as AS69-ApoE (22 kDa). The radiolabelled products 18F-AS69 and 18F-AS69-ApoE were successfully synthesised using the CFPRS system. Notably, 18F-AS69-ApoE showed higher BBB permeability than 18F-AS69 in an ex vivo study at 10 and 30 min post injection and was partially cleared from the brain at 120 min post injection. These results suggest that small, a brain shuttle peptide-fused fluorine-18 labelled protein binders can potentially be utilised for brain molecular imaging.
format	article
author	Takahiro Morito Ryuichi Harada Ren Iwata Yiqing Du Nobuyuki Okamura Yukitsuka Kudo Kazuhiko Yanai
author_facet	Takahiro Morito Ryuichi Harada Ren Iwata Yiqing Du Nobuyuki Okamura Yukitsuka Kudo Kazuhiko Yanai
author_sort	Takahiro Morito
title	Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody
title_short	Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody
title_full	Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody
title_fullStr	Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody
title_full_unstemmed	Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody
title_sort	synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1ed6b02705444b138a1da6dafa57c210
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Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody

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