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

• Published in: Molecular imaging and biology 2016-08, Vol.18 (4), p.598-605
• Main Authors: Fissers, Jens, Waldron, Ann-Marie, De Vijlder, Thomas, Van Broeck, Bianca, Pemberton, Darrel J., Mercken, Marc, Van Der Veken, Pieter, Joossens, Jurgen, Augustyns, Koen, Dedeurwaerdere, Stefanie, Stroobants, Sigrid, Staelens, Steven, wyffels, Leonie
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - metabolism; Animals; Antibodies, Monoclonal - immunology; Autoradiography; Brain - diagnostic imaging; Deferoxamine - chemistry; Humans; Imaging; Immunohistochemistry; Medicine; Medicine & Public Health; Mice, Inbred C57BL; Mice, Transgenic; Positron-Emission Tomography - methods; Radiology; Research Article; Staining and Labeling; Tissue Distribution; Zirconium - chemistry
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-016-0935-z

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 Aβ 1–40 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 Aβ 1–40 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 Aβ 1–40 . 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.