STUDY FREEZE-DRIED OF BEVACIZUMAB AND LABELING WITH 99mTc FOR TUMOR RADIOIMMUNOSCINTIGRAPHY
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Abstract
Objective: Bevacizumab, a humanized monoclonal antibody against VEGF was lyophilized and labeled with radioisotope 99mTc using in tumor radioimmunoscintigraphy. The purpose of the study is to develop a formulation and process for lyophilization of bevacizumab. Methods: Bevacizumab was studied on the lyophilization at the difference of buffers, pH, temperature and time. The antibody lyophilized compound was tested on the stable with time, radiolabeled with 99mTc radioisotope, radiochemical purity examination and stability of radioimmunoconjugates. Results: The results of the study showed that bevacizumab was lyophilized to form a white porous dry form under optimal conditions, as a phosphate buffer 0.5 M, pH 7.4 at -40 °C and a time of 24 hours. The lyophilized bevacizumab was stable after 6 months of follow-up. Radiochemical purity of 99mTc-bevacizumab has been reached more than 98 % and passed the test for sterility, bacterial endotoxin. Conclusion: Bevacizumab was prepared in a lyophilized formulation, can be used for radiolabeling with 99mTc, which met radiopharmaceutical criteria, and could be used in preclinical evaluations.
Keywords
Monoclonal antibody bevacizumab, radioisotope 99mTc, lyophilization radioimmunoscintigraphy
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References
2. Hongtao Li, Xiangdi Zhao, Jing Xie, Xingyu Zhu, Yue Su, Cuixia He et al., (2023). “A phase I study comparing the biosimilarity of the pharmacokinetics and safety of recombinant humanized anti-vascular endothelial growth factor monoclonal antibody injection with Avastin® in healthy Chinese male subjects”, BMC Pharmacol Toxicol, 24: 36,
doi:10.1186/s40360-023-00673-y.
3. Hui Tan, Jun Zhou, Xiangdong Yang, Dengfeng Cheng et al., (2017). “99mTc-labeled bevacizumab for detecting atherosclerotic plaque linked to plaque neovascularization and monitoring antiangiogenic effects of atorvastatin treatment in ApoE−/− mic”, Sci Rep, 7, 3504.
4. Bibi Faiza, Syed Qaiser Shah, (2020). “Synthesis of 99mTc‑p‑SCN‑Bzl‑TCMC‑bevacizumab for vascular endothelial growth factor (VEGF) receptor imaging using ovarian cancer model”, J Radioanal and Nucl Chem, 325(1). https:// doi.org/DOI:10.1007/s10967-020-07202-9.
5. Nguyễn Thị Khánh Giang, Nguyễn Thị Thu, Nguyễn Thị Ngọc và cộng sự, (2021). “Nghiên cứu đánh dấu kháng thể đơn dòng bevacizumab với đồng vị phóng xạ Tc-99m dùng trong chụp hình miễn dịch phóng xạ ung thư”, Tạp chí y dược lâm sàng 108, T10, p10-15.
6. British Pharmacopoeia 2016: European Pharmacopoeia monographs in accordance with Directive 98/34/EEC. https://Pharmacopoeia.com
7.https://ec.europa.eu/health/documents/communityregister/2018/20180124139952/anx_139952_en.pdf.
8. Henri Baudhuin, Pieter-Jan Van Bockstal, Thomas De Beer, Ilse Vaneycken, Jessica Bridoux, Geert Raes et al., (2021). “Lyophilization of NOTA-sdAbs: First step towards a cold diagnostic kit for 68Ga-labeling”, European Journal of Pharmaceutics and Biopharmaceutics, Volume 166, 194-204, https://doi.org/10.1016/j.ejpb.2021.06.012.
9. Taniwaki, L., Mendonça, R., Cunha-Júnior, A. S., Faraco, A. A. G., Ribeiro, J. A. S., Scott, I. U., & Jorge, R. (2010). “Effect of lyophilization on the in vitro biological activity of bevacizumab”, Eye, 24(10), 1628-1629. https://doi. org/10.1038/eye.2010.96.