Synthesis and Evaluation of a Zr-89-Labeled Monoclonal Antibody for Immuno-PET Imaging of Amyloid-β Deposition in the Brain View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-08

AUTHORS

Jens Fissers, Ann-Marie Waldron, Thomas De Vijlder, Bianca Van Broeck, Darrel J. Pemberton, Marc Mercken, Pieter Van Der Veken, Jurgen Joossens, Koen Augustyns, Stefanie Dedeurwaerdere, Sigrid Stroobants, Steven Staelens, Leonie wyffels

ABSTRACT

PURPOSE: The aim of this study was to evaluate the in vitro and in vivo characteristics of [(89)Zr]JRF/AβN/25, a radiolabeled monoclonal antibody directed against amyloid-β (Aβ). PROCEDURES: JRF/AβN/25 was labeled with (89)Zr following modification with desferal. The affinity of the tracer for Aβ1-40 was determined in a saturation binding assay. In vitro stability was evaluated, and in vivo plasma stability and biodistribution of [(89)Zr]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: [(89)Zr]Df-Bz-JRF/AβN/25 was obtained in an average radiochemical yield of 50 % and a radiochemical purity of >97 %. A saturation binding assay demonstrated specific binding of [(89)Zr]Df-Bz-JRF/AβN/25 to Aβ1-40 with nanomolar affinity. The tracer was stable in buffer and proved to be stable in vivo with >92 % 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, [(89)Zr]Df-Bz-JRF/AβN/25 demonstrated modest brain penetration, which slowly decreased in time. This cerebral uptake was confirmed by ex vivo autoradiography. CONCLUSIONS: [(89)Zr]Df-Bz-JRF/AβN/25 binds with high affinity to Aβ1-40. The tracer displays an acceptable in vivo stability and is able to cross the blood-brain barrier. [(89)Zr]Df-Bz-JRF/AβN/25 might therefore be a potential candidate for in vivo imaging of Aβ deposition in the brain. More... »

PAGES

598-605

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-016-0935-z

DOI

http://dx.doi.org/10.1007/s11307-016-0935-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049629522

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26846128


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