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

INTRODUCTION

Zirconium-89 (Zr, t=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 Zr-(LT) and Zr-(ST), and assessed the feasibility of Zr-(LT) for preclinical PET/CT.

METHODS

Zr-(ST) production was performed with an Y foil on a TR 19 cyclotron at 13.8MeV. For LT production; an aqueous solution of yttrium nitrate (Y(NO)·6HO) was irradiated on a TR 13 cyclotron at 12MeV. Zr 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 Zr-DFO-Trastuzumab from ST or LT with biodistribution analysis on day 5.

RESULTS

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 Zr-(ST) or Zr-(LT) was successful with purity>97% and specific activity>0.12MBq/μg (of antibody). MicroPET-CT imaging and biodistribution profiles showed similar uptake of Zr-(ST)-DFO-Trastuzumab and Zr-(LT)-DFO-Trastuzumab in tumor and all organs of interest.

CONCLUSION

Zr-(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 Zr produced from the two target systems.

ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE

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