Journal article
Zr-89-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo
The Journal of nuclear medicine (1978), Vol.60(5), pp.696-701
05/01/2019
DOI: 10.2967/jnumed.118.216457
PMCID: PMC6495241
PMID: 30442753
Abstract
Zr-89 immuno-PET continues to be assessed in numerous clinical trials. This report evaluates the use of Zr-89-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: Zr-89-DFO-trastuzumab and Zr-89-DFO- cetuximab were prepared using (ZrCl4)-Zr-89. 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) nacetyl- L-cysteine (NAC), or 0.25 M NaOAc containing 5 mg.mL(-1) L-methionine (L-MET). To assess antigen reactivity, Zr-89-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 (ZrCl4)-Zr-89, 89Zr-DFO-trastuzumab and Zr-89-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, Zr-89-DFO-trastuzumab remained reactive toward antigen after being prepared with (ZrCl4)-Zr-89. Conclusion: (ZrCl4)-Zr-89 facilitated the radiosynthesis of Zr-89 immuno-PET agents with increased specific activity. L-MET enhanced long-term solution stability better than all other formulations examined, and Zr-89-DFO- trastuzumab remained reactive toward antigen. Although further evaluation is necessary, these initial results suggest that (ZrCl4)-Zr-89 may be useful in immuno-PET radiochemistry as radiolabeled monoclonal antibodies are increasingly integrated into precision medicine strategies.
Details
- Title: Subtitle
- Zr-89-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo
- Creators
- Darpan N. Pandya - Wake Forest UniversityNikunj B. Bhatt - Wake Forest UniversityFrankis Almaguel - Wake Forest UniversityStephanie Rideout-Danner - Wake Forest UniversityHoward D. Gage - Wake Forest UniversityKiran Kumar Solingapuram Sai - Wake Forest UniversityThaddeus J. Wadas - Wake Forest University
- Resource Type
- Journal article
- Publication Details
- The Journal of nuclear medicine (1978), Vol.60(5), pp.696-701
- DOI
- 10.2967/jnumed.118.216457
- PMID
- 30442753
- PMCID
- PMC6495241
- NLM abbreviation
- J Nucl Med
- ISSN
- 0161-5505
- eISSN
- 1535-5667
- Publisher
- Soc Nuclear Medicine Inc
- Number of pages
- 6
- Grant note
- Wake Forest Innovations P30CA012197 / Translational Imaging Program - National Cancer Institute's Cancer Center Support Grant Wake Forest University Health Sciences R21CA219899 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA012197 / Tumor Tissue and Pathology Shared Resource - National Cancer Institute's Cancer Center Support Grant 2016-BIG-6524 / North Carolina Biotechnology Center Wake Forest Baptist Comprehensive Cancer Center Cell and Viral Vector Laboratory Shared Resource
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984312967302771
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