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

Introduction: Zirconium-89 (Zr-89, t(1/2) = 78.4 h) 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-89-(LT) and Zr-89-(ST), and assessed the feasibility of Zr-89-(LT) for preclinical PET/CT. Methods: Zr-89-(ST) production was performed with an Y-89 foil on a TR 19 cyclotron at 13.8 MeV. For LT production; an aqueous solution of yttrium nitrate (Y(NO3)(3) center dot 6H(2)O) was irradiated on a TR 13 cyclotron at 12 MeV. Zr-89 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 5 days post-injection of Zr-89-DFO-Trastuzumab from ST or LT with biodistribution analysis on day 5. Results: Irradiation of the ST yielded 2.88 +/- 1.07 GBq/mu A with a beam current of 14.0 +/- 3.8 mu A and irradiation time of 137 +/- 48 min at end of bombardment while LT yielded 0.27 0.05 GBq/mu A with a beam current of 9.9 +/- 22 mu A and irradiation time of 221 +/- 29 min. Radiolabeling of DFO-Trastuzumab with Zr-89-(ST) or Zr-89-(LT) was successful with purity > 97% and specific activity > 0.12 MBq/mu g (of antibody). MicroPET-CT imaging and biodistribution profiles showed similar uptake of Zr-89-(ST)-DFO-Trastuzumab and Zr-89-(LT)-DFO-Trastuzumab in tumor and all organs of interest. Conclusion: Zr-89-(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-89 produced from the two target systems. (C) 2017 Published by Elsevier Inc.