Abstract
The synthesis and investigation of a new bioconjugate for the targeted therapy of breast cancer is carried out. The ZHER2 scaffold polypeptide specific for the extracellular domain epitope of the HER2 transmembrane receptor, which is conjugated to a carrier molecule of human serum albumin (HSA) with the DOTA chelating agent attached to it, is used as the targeting agent. The radiolabeling reaction of the ZHER2–HSA–DOTA molecule is carried out with the 177Lu radionuclide, as well as with 212Pb, obtained using the developed laboratory generator. The radiochemical purity of the 177Lu-labeled preparation was 57 ± 10%, and that of the 212Pb-labeled preparation was 72 ± 5%. The degree of dissociative stability of these compounds was 73 ± 8% for 177Lu and more than 90% for 212Pb. In vitro tests of the cytotoxic activity of the obtained targeted radioactive compounds [177Lu]ZHER2–HSA–DOTA and [212Pb]ZHER2–HSA–DOTA in tumor-cell lines show a significant level of proliferation inhibition of the proliferation of human breast-cancer cells SK-BR-3 and BT474 with overexpression of the HER2/neu tumor marker in contrast to MCF-7 breast ductal adenocarcinoma cells with a low level of HER2/neu expression.
Similar content being viewed by others
REFERENCES
O. L. Polyanovskii, E. N. Lebedenko, and S. M. Deev, “ERBB-oncogene—proteins as targets for monoclonal antibodies,” Biochemistry (Moscow) 77, 227 (2012).
S. M. Deev, E. N. Lebedenko, L. E. Petrovskaya, D. A. Dolgikh, A. G. Gabibov, and M. P. Kirpichnikov, “Man-made antibodies and immunoconjugates with desired properties: Function optimization using structural engineering,” Russ. Chem. Rev. 84, 1 (2015). https://doi.org/10.1070/RCR4459
O. N. Shilova and S. M. Deev, “DARPins: Promising scaffolds for theranostics,” Acta Natur. 11 (4), 42 (2019).
A. Orlova, M. Magnusson, T. L. Eriksson, et al., “Tumor imaging using a picomolar affinity HER2 binding affibody molecule,” Cancer Res. 66, 4339 (2006). https://doi.org/10.1158/0008-5472.CAN-05-3521
S. M. Deyev, A. Vorobyeva, A. Schulga, et al., “Comparative evaluation of two DARPin variants: Effect of affinity, size and label on tumor targeting properties,” Mol. Pharm. 16, 995 (2019). https://doi.org/10.1021/acs.molpharmaceut.8b00922
D. Pilati and K. A. Howard, “Albumin-based drug designs for pharmacokinetic modulation,” Expert Opin Drug Metab. Toxicol. 16, 783 (2020). https://doi.org/10.1080/17425255.2020.1801633
W. A. Volkert and T. J. Hoffman, “Therapeutic radiopharmaceuticals,” Chem. Rev. 99, 2269 (1999). https://doi.org/10.1021/cr9804386
A. Dash, M. R. A. Pillai, and F. F. Knapp, Jr., “Production of 177Lu for targeted radionuclide therapy: Available options,” Nucl. Med. Mol. Imaging 49, 85 (2015). https://doi.org/10.1007/s13139-014-0315-z
F.-M. Su, P. Beaumier, D. Axworthy, et al., “Pretargeted radioimmunotherapy in tumored mice using an in vivo 212Pb/212Bi generator,” Nucl. Med. Biol. 32, 741 (2005). https://doi.org/10.1016/j.nucmedbio.2005.06.009
ACKNOWLEDGMENTS
This research was done according to agreement no. 598/KKFHT/313/1746-D.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
We declare that we have no conflicts of interest.
Additional information
Translated by D. Novikova
Rights and permissions
About this article
Cite this article
Artyukhov, A.A., Golovachenko, V.A., Deev, S.M. et al. Synthesis and Investigation of Radiopharmaceutical Complexes Based on 177Lu and 212Pb for the Targeted Therapy of Malignant Neoplasms. Nanotechnol Russia 17, 429–435 (2022). https://doi.org/10.1134/S2635167622030028
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S2635167622030028