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

Abstract

IntroductionZirconium-89 (89Zr, t1/2=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. Methods89Zr-(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. ResultsIrradiation 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. Conclusion89Zr-(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. Advances in knowledge and implications for patient careThese 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.