Implementation of ⁸⁹Zr production and in vivo imaging of B-cells in mice with ⁸⁹Zr-labeled anti B-cell antibodies by small animal PET/CT

Aim.
Labeling of specific monoclonal antibodies or their fragments with suitable radionuclides can be utilized for diagnosis of autoimmune disorders or in preclinical research for elucidation of the role of specific cell types in underlying disease pathophysiology. In contrast to other radionuclides, ⁸⁹Zr as a marker for positron emission tomography (PET) and protocols for ⁸⁹Zr production so far have found relatively little interest despite the many advantages of this radionuclide.
Methods.
We examined the production, separation, and characterization of ⁸⁹Zr, including supplementation of a commercial Cyclone^® 18/9 with a self-made Solid Target System (STS) and the construction of a re-usable target holder. Optimized conditions to reduce undesired long-lived side products were specified. Obtained [⁸⁹Zr]Zr-oxalate was used for labeling of anti-B cell antibodies with desferrioxamine-p-SCN as a bifunctional chelator. ⁸⁹Zr-labeled antibodies were injected in DBA/1 mice to examine usability for detection of B cells in vivo by PET.
Results.
The improved conditions yielded ⁸⁹Zr of high purity with smaller amounts of long living ⁸⁸Zr isotope compared to other methods. The antibody labeling procedure yielded crude mixtures containing non-chelated metal, which were separated using desalting columns. Analytical radio-HPLC and TLC revealed ⁸⁹Zr-labeled antibodies of sufficient purity. PET measurements showed binding of ⁸⁹Zr-labeled anti-B cell antibodies in tissues with high frequencies of B cells, i.e. in spleen and lymph nodes.
Conclusion.
Labeling of antibodies directed to specific cell types with ⁸⁹Zr according to our protocol turned out to be an effective tool for in vivo visualization and tracking of cells in mice by immuno-PET.