Publication
Title
Synthesis and evaluation of a Zr-89-labeled monoclonal antibody for immuno-PET imaging of amyloid- deposition in the brain
Author
Abstract
Purpose: The aim of this study was to evaluate the in vitro and in vivo characteristics of [89Zr]JRF/AβN/25, a radiolabeled monoclonal antibody directed against amyloid-β (Aβ). Procedures: JRF/AβN/25 was labeled with 89Zr following modification with desferal. The affinity of the tracer for Aβ140 was determined in a saturation binding assay. In vitro stability was evaluated, and in vivo plasma stability and biodistribution of [89Zr]Df-Bz-JRF/AβN/25 were determined in wild-type mice. To evaluate whether the antibody can cross the blood-brain barrier, brain uptake in wild-type mice was additionally assessed by ex vivo autoradiography. Results: [89Zr]Df-Bz-JRF/AβN/25 was obtained in an average radiochemical yield of 50 % and a radiochemical purity of 997 %. A saturation binding assay demonstrated specific binding of [89Zr]Df-Bz-JRF/AβN/25 to Aβ140 with nanomolar affinity. The tracer was stable in buffer and proved to be stable in vivo with 992 % intact monoclonal antibody (mAb) remaining in the plasma at 48 h post injection. A biodistribution study showed a slow blood clearance with no significant accumulation of activity in any of the organs. Furthermore, [89Zr]Df-Bz-JRF/AβN/25 demonstrated modest brain penetration, which slowly decreased in time. This cerebral uptake was confirmed by ex vivo autoradiography. Conclusions: [89Zr]Df-Bz-JRF/AβN/25 binds with high affinity to Aβ140. The tracer displays an acceptable in vivo stability and is able to cross the blood-brain barrier. [89Zr]Df-Bz-JRF/AβN/25 might therefore be a potential candidate for in vivo imaging of Aβ deposition in the brain.
Language
English
Source (journal)
Molecular imaging and biology. - Place of publication unknown
Publication
Place of publication unknown : 2016
ISSN
1536-1632
Volume/pages
18:4(2016), p. 598-605
ISI
000379191800015
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 29.07.2016
Last edited 12.11.2017
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