90Nb - a potential PET nuclide: production and labeling of monoclonal antibodies

Fast progressing immuno-PET gives reasons to develop new potential medium-long and long-lived radioisotopes. One of the promising candidates is Nb-90. It has a half-life of 14.6 h, which allows visualizing and quantifying processes with medium and slow kinetics, such as tumor accumulation of antibodies and antibodies fragments or polymers and other nanoparticles. Nb-90 exhibits a high positron branching of 53% and an optimal energy of beta(+) emission of E-mean = 0.35 MeV only. Consequently, efficient radionuclide production routes and Nb-V labeling techniques are required. Nb-90 was produced by the Zr-90(p,n)Nb-90 nuclear reaction on natural zirconium targets. No-carrier-added (n.c.a.) Nb-90 was separated from the zirconium target via a multi-step separation procedure including extraction steps and ion-exchange chromatography. Protein labeling was exemplified using the bifunctional chelator desferrioxamine attached to the monoclonal antibody rituximab. Desferrioxamine was coupled to rituximab via two different routes, by the use of N-succinyl-desferrioxamine (N-suc-Df) and by means of the bifunctional derivative p-isothiocyanatobenzyl-desferrioxarnine B (Df-Bz-NCS), respectively. Following antibody modification, labeling with Nb-90 was performed in HEPES buffer at pH 7 at room temperature. In vitro stability of the radiolabeled conjugates was tested in saline buffer at room temperature and in fetal calf serum (FCS) at 37 degrees C. The selected production route led to a high yield of 145 +/- 10 MBq/mu Ah of Nb-90 with high radioisotopic purity of >97%. This yield may allow for large scale production of about 10 GBq Nb-90. The separation procedure resulted in 76-81% yield. The Zr/Nb-90 decontamination factor reaches 10(7). Subsequent radiolabeling of the two different conjugates with Nb-90 gave high yields; after one hour incubation at room temperature, more than 90% of Nb-90-Df-mAb was formed in both cases. At room temperature in aqueous solution, both Nb-90-Df-mAb constructs were more than 99% stable over a period of 18d. The developed production and separation strategy provided Nb-90 with purity appropriate for radiolabeling applications. Labeling and stability studies proved the applicability of Nb-90 as a potential positron emitter for immuno-PET.