Zirconium-89 chloride can be used for immuno-PET radiochemistry without loss of antigen reactivity in vivo

摘要： Zirconium-89 (89Zr) immuno-PET continues to be assessed in numerous clinical trials. This report evaluates the use of zirconium-89 chloride (89Zr-ZrCl4) in the radiolabelling of monoclonal antibodies (mAbs) conjugated with desferrioxamine B (DFO), describes its effects on radiopharmaceutical reactivity toward antigen and offers guidance on how to ensure long-term stability and purity. Methods: 89Zr-Zr-DFO-trastuzumab and 89Zr-Zr-DFO-cetuximab were prepared using 89Zr-ZrCl4. The stability of each was evaluated for 7 days in 20 mM histidine/240 mM sucrose buffer, 0.25 M sodium acetate (NaOAc) buffer containing 5 mg?mL-1 n-acetyl-L-cysteine (NAC) or 0.25 M NaOAc containing 5 mg?mL-1 L-methionine (L-MET). To assess antigen reactivity, 89Zr-Zr-DFO-trastuzumab was evaluated using the Lindmo method and tested in PET/CT imaging of mouse models of human epidermal growth factor receptor 2 (HER2+/-) lung cancer. Results: Using 89Zr-ZrCl4, 89Zr-Zr-DFO-trastuzumab and 89Zr-Zr-DFO-cetuximab were prepared with increased specific activity and retained purities of 95% after 3 days when formulated in sodium acetate buffer containing L-MET. Based upon Lindmo analysis and small animal PET/CT imaging, 89Zr-Zr-DFO-trastuzumab remained reactive toward antigen after being prepared with 89Zr-ZrCl4. Conclusion: 89Zr-ZrCl4 facilitated the radiosynthesis of 89Zr-immuno-PET agents with increased specific activity. L-MET enhanced long-term solution stability better than all other formulations examined, and 89Zr-Zr- DFO-trastuzumab remained reactive toward antigen. While further evaluation is necessary, these initial results suggest that 89Zr-ZrCl4 may be useful in immuno-PET radiochemistry as radiolabeled mAbs are increasingly integrated into precision medicine strategies.