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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.

89Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo

⁸⁹Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo