⁸⁹Zr for antibody labeling and in vivo studies - A comparison between liquid and solid target production

Zirconium-89 (⁸⁹Zr, t_1/2=78.4h) liquid target (LT) production offers an approach to introduce this positron-emitting isotope to cyclotron centres without the need for a separate solid target (ST) production set up. We compared the production, purification, and antibody radiolabeling yields of ⁸⁹Zr-(LT) and ⁸⁹Zr-(ST), and assessed the feasibility of ⁸⁹Zr-(LT) for preclinical PET/CT.

⁸⁹Zr-(ST) production was performed with an ⁸⁹Y foil on a TR 19 cyclotron at 13.8MeV. For LT production; an aqueous solution of yttrium nitrate (Y(NO₃)₃·6H₂O) was irradiated on a TR 13 cyclotron at 12MeV. ⁸⁹Zr was purified from the ST or LT material with hydroxamate resin, and used to radiolabel p-SCN-Bn-Deferoxamine (DFO)-conjugated Trastuzumab. MicroPET-CT imaging was performed at 1, 3 and 5days post-injection of ⁸⁹Zr-DFO-Trastuzumab from ST or LT with biodistribution analysis on day 5.

Irradiation of the ST yielded 2.88±1.07GBq/μA with a beam current of 14.0±3.8μA and irradiation time of 137±48min at end of bombardment while LT yielded 0.27±0.05GBq/μA with a beam current of 9.9±2.2μA and irradiation time of 221±29min. Radiolabeling of DFO-Trastuzumab with ⁸⁹Zr-(ST) or ⁸⁹Zr-(LT) was successful with purity>97% and specific activity>0.12MBq/μg (of antibody). MicroPET-CT imaging and biodistribution profiles showed similar uptake of ⁸⁹Zr-(ST)-DFO-Trastuzumab and ⁸⁹Zr-(LT)-DFO-Trastuzumab in tumor and all organs of interest.

⁸⁹Zr-(LT) was effectively used to prepare antibody bioconjugates with specific activities suitable for small animal imaging. PET imaging and biodistribution revealed similar behaviours between bioconjugates labeled with ⁸⁹Zr produced from the two target systems.

These results have important implications for the production of PET isotopes such as ⁸⁹Zr to cyclotron facilities with only LT capabilities - such as most clinical centres - expanding the availability of ⁸⁹Zr-immunoPET.