Separation of ⁹⁰Nb from zirconium target for application in immuno-PET

Abstract

Fast progressing immuno-PET asks to explore new radionuclides. One of the promising candidates is 90 Nb. It has a half-life of 14.6 h that allows visualizing and quantifying biological processes with medium and slow kinetics, such as tumor accumulation of antibodies and antibodies fragments or drug delivery systems and nanoparticles. 90 Nb exhibits a positron branching of 53% and an average kinetic energy of emitted positrons of mean = 0.35 MeV. Currently, radionuclide production routes and Nb V labeling techniques are explored to turn this radionuclide into a useful imaging probe. However, efficient separation of 90 Nb from irradiated targets remains in challenge.Ion exchange based separation of 90 Nb from zirconium targets was investigated in systems AG 1 × 8 -HCl/H 2 O 2 and UTEVA-HCl. 95 Nb ( 1/2 = 35.0 d), 95 Zr ( 1/2 = 64.0 d) and 92m Nb ( 1/2 = 10.15 d) were chosen for studies on distribution coefficients. Separation after AG 1 × 8 anion exchange yields 99% of 90/95 Nb. Subsequent use of a solidphase extraction step on UTEVA resin further decontaminates 90/95 Nb from traces of zirconium with yields 95% of 90/95 Nb.A semi-automated separation takes one hour to obtain an overall recovery of 90/95 Nb of 90%. The amount of Zr was reduced by factor of 10 8 . The selected separation provides rapid preparation (< 1 h) of high purity 90 Nb appropriate for the synthesis of 90 Nb-radiopharmaceuticals, relevant for purposes of immuno-PET. Applying the radioniobium obtained, 90/95 Nb-labeling of a monoclonal antibody (rituximab) modified with desferrioxamine achieved labeling yields of > 90% after 1 h incubation at room temperature.

Determination of distribution coefficients (Kd) of various radionuclides on UTEVA resin

“…Zr, Y and Nb were separated from each other with the following eluates: 9 M HCl elutes Y, 4.5 M HCl elutes Zr and 2 M HCl elutes Nb. The data from Nb, Zr, Y separation is consistent with the results for K d in the current publication and previously published results of Nb and Zr separations [2]. A small niobium peak and the remaining 10% of Nb on the resin are probably due to hydrolysis of Nb (Figure 8).…”

“…It is apparent that Ba, Sr and Co passed through the resin without any retention. The values of the distribution coefficients for Nb in the high HCl concentration cocktail differ from previously published data [2]. The difference of K d values could be explained by hydrolysis due to the evaporation process (e. g. NbO 3+ complexes) or by partial dissolution of the extractant in the aqueous phase [21,22].…”

“…The separation with hydrochloric acid was carried out for 95 Nb, 88 Zr and 88 Y and compared with previously published data [2]. The separation was performed with initial cocktail solutions of 95 Nb, 88 Zr and 88 Y and subsequently evaporated to dryness and then dissolved in 9 M of HCl.…”

Direct flow separation strategy, to isolate no-carrier-added90Nb from irradiated Mo or Zr targets

“…The crude separation from Zr or Mo target was applied following a published protocol [31]. Zr/Nb and Mo/Nb was measured by ICP-MS and -ray.…”

“…We were able to provide proof-of-principle by labeling 90 Nb with the monoclonal antibody (mAb) Rituximab and demonstrating high labeling yields as well as stability of the labeled mAb [30]. After demonstrating the potential of 90 Nb in a proof-of-principle study, we continued with the development of efficient separation strategies to isolate 90 Nb from irradiated zirconium targets, to provide adequate radionuclidic and radiochemical purity for subsequent application for immuno-PET [31]. There is significant amount of literature on separation methods for Zr and Nb, mainly for the purposes of separation of uranium fission products: 95 Zr/ 95 Nb.…”