Startseite Astatine-211 labelled a small molecule peptide: specific cell killing in vitro and targeted therapy in a nude-mouse model
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Astatine-211 labelled a small molecule peptide: specific cell killing in vitro and targeted therapy in a nude-mouse model

  • Weihao Liu , Yu Tang , Huan Ma , Feize Li , Yingjiang Hu , Yuanyou Yang EMAIL logo , Jijun Yang , Jiali Liao und Ning Liu EMAIL logo
Veröffentlicht/Copyright: 18. Dezember 2020
Radiochimica Acta
Aus der Zeitschrift Radiochimica Acta Band 109 Heft 2

Abstract

Extensive interest in the development of α-emitting radionuclides astatine-211 (211At) stems from the potential superiority for the treatment of smaller tumors, disseminated disease, and metastatic disease. VP2, a small molecule fusion peptide, can specifically bind to the VPAC1 receptor which is over-expressed in malignant epithelial tumors. In our recent study, we performed the preparation of 211At labelled VP2 through a one-step method. In this work, we explored the targeted radionuclide therapy with [211At]At-SPC-VP2 in vitro and in vivo. The cytotoxicity and specific cell killing of [211At]At-SPC-VP2 were evaluated using the CCK-8 assay. Compared with the [211At]NaAt, the VPAC1-targeted radionuclide compound [211At]At-SPC-VP2 showed more effective cytotoxicity in vitro. Targeted radioactive therapy trial was carried out in non-small-cell lung cancer (NSCLC) xenograft mice. For the therapy experiment, 4 groups of mice were injected via the tail vein with 370 kBq, 550 kBq, 740 kBq, 3 × ∼246 kBq of [211At]At-SPC-VP2, of which the second and third injections were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with saline or 550 kBq [211At]NaAt. The body weight and tumor size of mice were monitored before the administration and every 2 days thereafter. Cytotoxic radiation of partial tissue samples such as kidneys, liver and stomach of mice were assessed by immunohistochemical examination. The tumor growth was inhibited and significantly improved survival was achieved in mice treated with [211At]At-SPC-VP2, two-fold prolongation of survival compared with the control group, which received normal saline or 550 kBq [211At]NaAt. No renal or hepatic toxicity was observed in the mice receiving [211At]At-SPC-VP2, but gastric pathological sections showed 211At uptake in stomach resulting in later toxicity, highlighting the importance of further enhancing the stability of labelled compounds.

Keywords: astatine-211; cell killing; pathological section; targeted therapy; VP2
Corresponding authors: Yuanyou Yang and Ning Liu, Key Laboratory of Radiation Physics and Technology (Sichuan University), Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu610064, China, E-mail: (N. Liu), (Y. Yang)

Funding source: China National Natural Science Foundation

Award Identifier / Grant number: 21371124

Funding source: Key Technology Research and Development Program of Sichuan Province (China)

Award Identifier / Grant number: 2018SZ0022

Funding source: Major Science and Technology Projects of Sichuan Province (China)

Award Identifier / Grant number: 2019ZDZX0004

Acknowledgments

This work was financially supported by the China National Natural Science Foundation (Grant No. 21371124), Key Technology Research and Development Program of Sichuan Province (China) (Grant no. 2018SZ0022) and Major Science and Technology Projects of Sichuan Province (China) (Grant NO. 2019ZDZX0004). We would like to thank the cyclotron operation crew Xiaodong Liao of Sichuan University for his help in performing irradiations.

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was financially supported by the China National Natural Science Foundation (Grant no. 21371124), Key Technology Research and Development Program of Sichuan Province (China) (Grant no. 2018SZ0022) and Major Science and Technology Projects of Sichuan Province (China) (Grant no. 2019ZDZX0004).

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Makvandi, M., Dupis, E., Engle, J. W., Nortier, F. M., Fassbender, M. E., Simon, S., Birnbaum, E. R., Atcher, R. W., John, K. D., Rixe, O., Norenbeng, J. P. Alpha-emitters and targeted alpha therapy in oncology: from basic science to clinical investigations. Targeted Oncol. 2018, 13, 189; https://doi.org/10.1007/s11523-018-0550-9.Suche in Google Scholar PubMed

2. Zukotynski, K., Jadvar, H., Capala, J., Fahey, F. Targeted radionuclide therapy: practical applications and future prospects. Biomark. Cancer 2016, 8(S2), 35; https://doi.org/10.4137/BIC.S31804.Suche in Google Scholar PubMed PubMed Central

3. Jadvar, H. Targeted radionuclide therapy: an evolution toward precision cancer treatment. Am. J. Roentgenol. 2017, 209, 277; https://doi.org/10.2214/ajr.17.18264.Suche in Google Scholar

4. Eriksson, S. E., Elgstro, E., Back, T., Ohlsson, T., Jensen, H., Nilsson, R., Lingdegren, S., Tennvall, J. Sequential radioimmunotherapy with 117Lu-and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model. Cancer Biother. Radiopharm. 2014, 29, 238; https://doi.org/10.1089/cbr.2014.1625.Suche in Google Scholar PubMed

5. Kim, Y. S., Brechbiel, M. W. An overview of targeted alpha therapy. Tumor Biol. 2012, 33, 573; https://doi.org/10.1007/s13277-011-0286-y.Suche in Google Scholar PubMed PubMed Central

6. Sathekge, M., Vorster, M., Knoesen, O., Meckel, M., Modiselle, M., Marx, S. 213Bi-PSMA-617 targeted alpha-radionuclide therapy in metastatic castration-resistant prostate cancer. Eur. J. Nucl. Med. Mol. Imag. 2017, 44, 1099; https://doi.org/10.1007/s00259-017-3657-9.Suche in Google Scholar PubMed PubMed Central

7. Lucignani, G. Alpha-particle radioimmunotherapy with astatine-211 and bismuth-213. Eur. J. Nucl. Med. Mol. Imag. 2008, 35, 1729; https://doi.org/10.1007/s00259-008-0856-4.Suche in Google Scholar PubMed

8. Chérel, M., Gouard, S., Gaschet, J., Saï-Maurel, C., Bruchertseifer, F., Alfred Morgenstern, A., Bourgeois, M., Gestin, J. F., Bodéré, F. K., Barbet, J., Moreau, P., Davodeau, F. 213Bi radioimmunotherapy with an anti-mCD138 monoclonal antibody in a murine model of multiple myeloma. J. Nucl. Med. 2013, 54, 1597; https://doi.org/10.2967/jnumed.112.111997.Suche in Google Scholar PubMed

9. Ming, H., Fang, L., Gao, J., Li, C., Ji, Y., Shen, Y., Hu, Y., Li, N., Chang, J., Li, W., Tan, J. 131I-Labeled arginine-glycine-aspartate-bovine serum albumin-polycaprolactone in lung cancer. AJR Am. J. Roentgenol. 2017, 208, 1116.10.2214/AJR.16.16947Suche in Google Scholar PubMed

10. Lucas, S., Feron, O., Gallez, B., Masereel, B., Michiels, C., Borght, T. V. Monte Carlo calculation of radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re- nanoobjects: choice of the best radionuclide for solid tumor treatment by using TCP and NTCP concepts. Comput. Math. Meth. Med. 2007, 2015, 284360.10.1155/2015/284360Suche in Google Scholar

11. Fujiwara, K., Koyama, K., Suga, K., Ikemura, M., Saito, Y., Hino, A., Hiroko Iwanari, H., Kusano-Arai, O., Mitsui, K., Kasahara, H., Fukayama, M., Kodama, T., Hamakubo, T., Momose, T. 90Y-labeled anti-ROBO1 monoclonal antibody exhibits antitumor activity against small cell lung cancer xenografts. PloS One 2015, 10, e0125468; https://doi.org/10.1371/journal.pone.0125468.Suche in Google Scholar PubMed PubMed Central

12. Erlandsson, A., Forssell-Aronsson, E., Seidal, T., Bernhardt, P. Binding of TS1, an anti-keratin 8 antibody, in small-cell lung cancer after 177Lu-DOTA-Tyr3-octreotate treatment: a histological study in xenografted mice. EJNMMI Res. 2011, 1, 19; https://doi.org/10.1186/2191-219x-1-19.Suche in Google Scholar PubMed PubMed Central

13. Nikolic, N., Vranjes-Djuric, S. D., Jankovic, D. L. Modified 90Y-hydroxyapatite microparticles, possible agent for lung cancer therapy. Nucl. Med. Biol. 2010, 37, 696; https://doi.org/10.1016/j.nucmedbio.2010.04.167.Suche in Google Scholar

14. Wang, H., Cao, C., Li, B., Chen, S., Yin, J., Shi, J., Ye, D., Tao, Q., Hu, P., Epstein, A., Ju, D. Immunogenicity of Iodine 131I chimeric tumor necrosis therapy monoclonal antibody in advanced lung cancer patients. Cancer Immunol. Immunother. 2008, 57, 677; https://doi.org/10.1007/s00262-007-0406-0.Suche in Google Scholar PubMed

15. Chen, S., Yu, L., Jian, C., Zhao, Y., Sun, D., Li, S., Liao, G., Chen, Y., Fu, Q., Tao, Q., Ye, D., Hu, P., Khawli, L. A., Taylor, C. R., Epstein, A. L., Ju, D. W. Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer. J. Clin. Oncol. 2005, 23, 1538; https://doi.org/10.1200/jco.2005.06.108.Suche in Google Scholar PubMed

16. Li, W., Liu, Z., Li, C., Li, N., Fang, L., Chang, J., Tan, J. Radionuclide therapy using 131I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression. J. Cancer Res. Clin. Oncol. 2007, 142, 619.10.1007/s00432-015-2067-2Suche in Google Scholar PubMed

17. Crawford, L. M. New therapy for non-Hodgkin lymphoma. J. Am. Med. Assoc. 2002, 287, 13.10.1001/jama.287.13.1640Suche in Google Scholar

18. Iagaru, A., Mittra, E. S., Ganjoo, K., Knox, S. J., Goris, M. L. 131I-Tositumomab (Bexxar) vs. 90Y-Ibritumomab (Zevalin) therapy of low-grade refractory/relapsed non-Hodgkin lymphoma. Mol. Imag. Biol. 2010, 12, 198; https://doi.org/10.1007/s11307-009-0245-9.Suche in Google Scholar PubMed

19. Goldsmith, S. J. Radioimmunotherapy of lymphoma: Bexxar and Zevalin. Semin. Nucl. Med. 2010, 40, 122; https://doi.org/10.1053/j.semnuclmed.2009.11.002.Suche in Google Scholar PubMed

20. Strosberg, J., El-Haddad, G., Wolin, E., Hendifar, A., Yao, J., Chasen, B., Mittra, E., Kunz, P. L., Kulke, M. H., Jacene, H., Bushnell, D., O’Dorisio, T. M., Baum, R. P., Kulkarni, H. R., Caplin, M., Lebtahi, R., Hobday, T., Delpassand, E., Van, C. E., Benson, A., Srirajaskanthan, R., Pavel, M., Mora, J., Berlin, J., Grande, E., Reed, N., Seregni, E., Öberg, K., Lopera, S. M., Santoro, P., Thevenet, T., Erion, J. L., Ruszniewski, P., Kwekkeboom, D., Krenning, E. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumor. N. Engl. J. Med. 2017, 376, 125; https://doi.org/10.1056/nejmoa1607427.Suche in Google Scholar PubMed PubMed Central

21. Witzig, T. E., Flinn, I. W., Gordon, L. I., Emmanouilides, C., Czuczman, M. S., Saleh, M. N., Cripe, L., Wiseman, G., Olejnik, T., Multani, P. S., White, C. A. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab refractory follicular non-Hodgkin’s lymphoma. J. Clin. Oncol. 2002, 20, 3262; https://doi.org/10.1200/jco.2002.11.017.Suche in Google Scholar PubMed

22. Winter, J. N., Dnwards, D. J., Spies, S., Wiseman, G., Patton, D., Erwin, W., Rademaker, A. W., Weitner, B. B., Williams, S. F., Tallman, M. S., Micallef, I., Mehta, J., Singhal, S., Evens, A. M., Zimmer, M., Molina, A., White, C. A., Gordon, L. I. Yttrium-90 ibritumomab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with high-dose BEAM and autologous transplantation in relapsed or refractory B-cell non-Hodgkin’s lymphoma. J. Clin. Oncol. 2009, 27, 1653; https://doi.org/10.1200/jco.2008.19.2245.Suche in Google Scholar PubMed PubMed Central

23. Green, D. J., Shadman, M., Jones, J. C., Frayo, S. L., Kenoyer, A. L., Hylarides, M. D., Hamlin, D. K., Wilbur, D. S., Balkan, E. R., Lin, Y., Miller, B. W., Frost, S. H., Gopal, A. K., Orozco, J. J., Gooley, T. A., Laird, K. L., Till, B. G., Back, T., Sandmaier, B. M., Pagel, J. M., Press, O. W. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model. Blood 2015, 125, 2111; https://doi.org/10.1182/blood-2014-11-612770.Suche in Google Scholar PubMed PubMed Central

24. Kojima, S., Cuttler, J. M., Shimura, N., Koga, H., Murata, A., Kawashima, A. Present and future prospects of radiation therapy using alpha-emitting nuclides. Dose Response 2018, 16, 1; https://doi.org/10.1177/1559325817747387.Suche in Google Scholar PubMed PubMed Central

25. Dekempeneer, Y., Keyaerts, M., Krasniqi, A., Puttemans, J., Muyldermans, S., Lahoutte, T., D’huyvetter, M., Devoogdt, M. Targeted alpha therapy using short-lived alpha-particles and the promise of nanobodies as targeting vehicle. Expet. Opin. Biol. Ther. 2016, 16, 1035; https://doi.org/10.1080/14712598.2016.1185412.Suche in Google Scholar PubMed PubMed Central

26. Zalutsky, M. R., Zhao, X. G., Alston, K. L., Bigner, D. High-level production of α-particle–emitting 211At and preparation of 211At-Labelled antibodies for clinical use. J. Nucl. Med. 2001, 42, 1508.Suche in Google Scholar

27. Zalutsky, M. R., Bigner, D. D. Radioimmunotherapy with α-particle emitting radioimmunoconjugates. Acta Oncol. 2009, 35, 373; https://doi.org/10.3109/02841869609101654.Suche in Google Scholar PubMed

28. Dadachova, E. Cancer therapy with alpha-emitters labelled peptides. Semin. Nucl. Med. 2010, 40, 204; https://doi.org/10.1053/j.semnuclmed.2010.01.002.Suche in Google Scholar PubMed

29. Larsen, R. H., Murud, K. M., Akabani, G., Hoff, P., Bruland, O. S., Zalutsky, M. R. 211At- and 131I- labeled bisphosphonates with high in vivo stability and bone accumulation. J. Nucl. Med. 1998, 40, 1197.Suche in Google Scholar

30. Pruszynski, M., Bilewicz, A., Zalutsky, M. R. Preparation of Rh[16aneS4-diol]211At and Ir[16aneS4-diol]211At complexes as potential precursors for astatine radiopharmaceuticals. Part I: synthesis, bioconjugate. Inside Chem. 2008, 19, 958.10.1021/bc700413rSuche in Google Scholar PubMed PubMed Central

31. Zhao, B., Qin, S., Chai, L., Lu, G., Yang, Y., Cai, H., Yuan, X., Fan, S., Huang, Q., Yu, F. Evaluation of astatine-211-labeled octreotide as a potential radiotherapeutic agent for NSCLC treatment. Bioorg. Med. Chem. 2018, 26, 1086; https://doi.org/10.1016/j.bmc.2018.01.023.Suche in Google Scholar PubMed

32. Kozempel, J., Mokhodoeva, O., Vlk, M. Progress in targeted alpha-particle therapy. What we learned about recoils release from in vivo generators. Molecules 2018, 23, 581; https://doi.org/10.3390/molecules23030581.Suche in Google Scholar PubMed PubMed Central

33. Laburthe, M., Couvineau, A., Tan, V. Class II G protein-coupled receptors for VIP and PACAP: structure, models of activation and pharmacology. Peptides 2007, 28, 1631; https://doi.org/10.1016/j.peptides.2007.04.026.Suche in Google Scholar PubMed

34. Reubi, J. C., Korner, M., Waser, B., Mazzucchelli, L., Guillou, L. High expression of peptide receptors as a novel target in gastrointestinal stromal tumors. Eur. J. Nucl. Med. Mol. Imag. 2004, 31, 803; https://doi.org/10.1007/s00259-004-1476-2.Suche in Google Scholar PubMed

35. Valdehita, A., Bajo, A. M., Schally, A. V., Varga, J. L., Carmena, M. J., Prieto, J. C. Vasoactive intestinal peptide (VIP) induces transactivation of EGFR and HER2 in human breast cancer cells. Mol. Cell. Endocrinol. 2009, 302, 41; https://doi.org/10.1016/j.mce.2008.11.024.Suche in Google Scholar PubMed

36. Tang, B., Li, Z., Huang, D., Zheng, L., Li, Q. Screening of a specific peptide binding to VPAC1 receptor from a phage display peptide library. PloS One 2013, 8, 54264; https://doi.org/10.1371/journal.pone.0054264.Suche in Google Scholar PubMed PubMed Central

37. Liu, W., Ma, H., Tang, Y., Chen, Q., Peng, S., Yang, J. One-step labelling of a novel small-molecule peptide with astatine-211: preliminary evaluation in vitro and in vivo. J. Radioanal. Nucl. Chem. 2018, 316, 451; https://doi.org/10.1007/s10967-018-5780-x.Suche in Google Scholar

38. Yang, Y., Liu, N., Liao, J., Pu, M., Liu, Y., Wei, M., Jin, J. Preparation and preliminary evaluation of 211At-labeled amidobisphophonates. J. Radioanal. Nucl. Chem. 2010, 283, 329; https://doi.org/10.1007/s10967-009-0384-0.Suche in Google Scholar

39. Elgqvist, J., Andersson, H., Back, T., Claesson, I., Hultborn, R., Jensen, H., Lindegren, S., Olsson, M., Palm, S., Warnhammar, E., Jacobsson, L. Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab’)2: therapeutic efficacy and myelotoxicity. Nucl. Med. Biol. 2006, 33, 1065; https://doi.org/10.1016/j.nucmedbio.2006.07.009.Suche in Google Scholar PubMed

40. Zuconellia, C. R., Brocka, R., Adjobo-Hermans, M. J. W. Linear peptides in intracellular applications. Curr. Med. Chem. 2017, 24, 1; https://doi.org/10.2174/0929867324666170508143523.Suche in Google Scholar PubMed

41. Nischan, N., Chakrabarti, A., Serwa, A. R., Bovee-Geurts, P. H. M., Brock, R., Hackenberger, C. P. R. Stabilization of peptides for intracellular applications by phosphoramidate-linked polyethylene glycol chains. Angew. Chem. Int. Ed. 2013, 52, 11920; https://doi.org/10.1002/anie.201303467.Suche in Google Scholar PubMed

Received: 2020-03-09
Accepted: 2020-11-16
Published Online: 2020-12-18
Published in Print: 2021-02-23

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Original Papers
  3. Sorption and surface complexation modeling of 137Cs on Fe(II)-montmorillonite clay mineral relevant to nuclear waste disposal
  4. Kinetics and adsorption equilibrium of some radionuclides on polyaniline/SiO2 composite
  5. Adsorption from liquid metals: an approach for recovery of radionuclides from irradiated targets
  6. Radioiodination and biological evaluation of Cimetidine as a new highly selective radiotracer for peptic ulcer disorder detection
  7. Astatine-211 labelled a small molecule peptide: specific cell killing in vitro and targeted therapy in a nude-mouse model
  8. Impact of foaming agent and nanoparticle fillers on the properties of irradiated rubber
  9. Development of SiO2 based doped with LiF, Cr2O3, CoO4 and B2O3 glasses for gamma and fast neutron shielding
https://doi.org/10.1515/ract-2020-0016
Schlagwörter für diesen Artikel
astatine-211; cell killing; pathological section; targeted therapy; VP2

Artikel in diesem Heft

  1. Frontmatter
  2. Original Papers
  3. Sorption and surface complexation modeling of 137Cs on Fe(II)-montmorillonite clay mineral relevant to nuclear waste disposal
  4. Kinetics and adsorption equilibrium of some radionuclides on polyaniline/SiO2 composite
  5. Adsorption from liquid metals: an approach for recovery of radionuclides from irradiated targets
  6. Radioiodination and biological evaluation of Cimetidine as a new highly selective radiotracer for peptic ulcer disorder detection
  7. Astatine-211 labelled a small molecule peptide: specific cell killing in vitro and targeted therapy in a nude-mouse model
  8. Impact of foaming agent and nanoparticle fillers on the properties of irradiated rubber
  9. Development of SiO2 based doped with LiF, Cr2O3, CoO4 and B2O3 glasses for gamma and fast neutron shielding
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