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Title
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Synthesis and evaluation of a Zr-89-labeled monoclonal antibody for immuno-PET imaging of amyloid- deposition in the brain
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Molecular imaging and biology. - Place of publication unknown
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Publication
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Place of publication unknown
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2016
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ISSN
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1536-1632
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DOI
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10.1007/S11307-016-0935-Z
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Volume/pages
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18
:4
(2016)
, p. 598-605
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ISI
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000379191800015
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Pubmed ID
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26846128
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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