RT Journal Article
SR Electronic
T1 <sup>89</sup>Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 696
OP 701
DO 10.2967/jnumed.118.216457
VO 60
IS 5
A1 Pandya, Darpan N.
A1 Bhatt, Nikunj B.
A1 Almaguel, Frankis
A1 Rideout-Danner, Stephanie
A1 Gage, Howard D.
A1 Solingapuram Sai, Kiran Kumar
A1 Wadas, Thaddeus J.
YR 2019
UL http://jnm.snmjournals.org/content/60/5/696.abstract
AB 89Zr immuno-PET continues to be assessed in numerous clinical trials. This report evaluates the use of 89Zr-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: 89Zr-DFO-trastuzumab and 89Zr-DFO-cetuximab were prepared using 89ZrCl4. 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, 89Zr-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 89ZrCl4, 89Zr-DFO-trastuzumab and 89Zr-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, 89Zr-DFO-trastuzumab remained reactive toward antigen after being prepared with 89ZrCl4. Conclusion: 89ZrCl4 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-DFO-trastuzumab remained reactive toward antigen. Although further evaluation is necessary, these initial results suggest that 89ZrCl4 may be useful in immuno-PET radiochemistry as radiolabeled monoclonal antibodies are increasingly integrated into precision medicine strategies.