Comparison study on radiolabeling antibodies with ⁸⁹Zr produced from solid and liquid target systems

Objectives Zirconium-89 (⁸⁹Zr) is an attractive radioisotope for radiolabeling of monoclonal antibodies (mAb). Our group has produced ⁸⁹Zr using both solid and salt-solution (liquid) yttrium (Y) targets. The aim of this study was to assess and compare antibody radiolabeling yields between ⁸⁹Zr produced from different target systems.

Methods Two solid target (ST) ⁸⁹Y discs, each 10 mm diameter with 99.9% purity but different thicknesses (disc 1 (ST1): 1.016 mm 0.356 g and disc 2 (ST2) 0.254 mm, 0.087 g) were bombarded with 13.9 MeV protons for 40 min (800 μA.min). The liquid target (LT) material consisted of 2.75M natY(NO₃)₃ in nitric acid (1M) with a yttrium purity of 99.9% and density of 1.49 g/mL, were bombarded for 60 min with 13 MeV protons (426 μA.min). Dissolved ST discs and the LT solution were adjusted to 2M with HCl and purified by the same batch of hydroxamate resin. Zr chelator, deferoxamine (Df) was conjugated to mAb (3:1 ratio) and purified by centrifugation. Antibody labeling was performed in HEPES buffer (0.5 M, pH 7.1) at room temperature overnight with a mAb-Df concentration of 0.9 mg/mL (ST1 and ST2) or 0.3 mg/mL (LT). Radiolabeling yields were determined after PD-10 column purification.

Results End of bombardment yields for ⁸⁹Zr were 696 MBq (ST1), 420 MBq (ST2) and 13.6 MBq (LT). ⁸⁹Zr eluted from the hydroxamate resin using 3x0.5mL 1M oxalic acid with 453 MBq (ST1), 385 MBq (ST2) and 10.4 MBq (LT) respectively eluting within the first 0.5 mL. Radiolabeling of mAb-Df used 7.2 MBq, 20uL (ST1), 6.7 MBq, 20uL (ST2) and 7.8 MBq, 0.5mL (LT) of ⁸⁹Zr-oxalate with yields of 80% (ST1), 79% (ST2) and 68% (LT).

Conclusions Successful mAb labeling was achieved with ⁸⁹9Zr produced from all target systems. Slightly lower radiolabeling yield from ⁸⁹Zr produced by liquid target might be due to dilution of mAb-Df in the LT reaction caused by a lower ⁸⁹Zr-oxalate concentration.