Abstract
(89)Zr immuno-PET continues to be assessed in numerous clinical trials. This report evaluates the use of (89)Zr-chloride in the radiolabeling of monoclonal antibodies 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:(89)Zr-DFO-trastuzumab and (89)Zr-DFO-cetuximab were prepared using (89)ZrCl(4) The stability of each was evaluated for 7 d 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, (89)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-positive or -negative lung cancer. Results: Using (89)ZrCl(4), (89)Zr-DFO-trastuzumab and (89)Zr-DFO-cetuximab were prepared with increased specific activity and retained purities of 95% after 3 d when formulated in NaOAc buffer containing L-MET. Based on Lindmo analysis and small-animal PET/CT imaging, (89)Zr-DFO-trastuzumab remained reactive toward antigen after being prepared with (89)ZrCl(4)Conclusion:(89)ZrCl(4) facilitated the radiosynthesis of (89)Zr immuno-PET agents with increased specific activity. L-MET enhanced long-term solution stability better than all other formulations examined, and (89)Zr-DFO-trastuzumab remained reactive toward antigen. Although further evaluation is necessary, these initial results suggest that (89)ZrCl(4) may be useful in immuno-PET radiochemistry as radiolabeled monoclonal antibodies are increasingly integrated into precision medicine strategies.