Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Validation of the production quality and therapeutic efficacy of 47Sc through its anti-cancer effects against EGFR-targeted non-small cell lung cancer

  • Da-Mi Kim (Radioisotope Research Division, Department of Quantum and Convergence Sciences, Korea Atomic Energy Research Institute) ;
  • So-Young Lee (Radioisotope Research Division, Department of Quantum and Convergence Sciences, Korea Atomic Energy Research Institute) ;
  • Jae-Cheong Lim (Radioisotope Research Division, Department of Quantum and Convergence Sciences, Korea Atomic Energy Research Institute) ;
  • Eun-Ha Cho (Radioisotope Research Division, Department of Quantum and Convergence Sciences, Korea Atomic Energy Research Institute) ;
  • Ul-Jae Park (Radioisotope Research Division, Department of Quantum and Convergence Sciences, Korea Atomic Energy Research Institute)
  • Received : 2022.04.13
  • Accepted : 2022.06.24
  • Published : 2022.06.30
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Abstract

Anti-cancer and therapeutic effects using therapeutic radioisotopes have been demonstrated by various studies, and it is well-known that therapeutic radioisotopes are useful in cancer treatment. Recently, one of the therapeutic radioisotopes, scandium is emerging as a radioisotope applicable to PET imaging (43Sc, 44Sc) and therapy (47Sc) in cancer theranostic approach. However, 47Sc has little known radiobiological and therapeutic efficacy compared to other therapeutic radioisotopes. Here, we investigated the quality and therapeutic efficacy of 47Sc radioisotope produced by our production/isolation technology at the research reactor 'HANARO' in KAERI (Korea Atomic Energy Research Institute). We showed that the therapeutic efficacy of 47Sc, produced by our production/isolation technology, effectively suppressed epidermal growth factor receptor (EGFR)-targeted non-small cell lung cancer (NSCLC) cells. Consequently, these results suggest that the high quality of the produced 47Sc by our production/isolation technology enables the development of therapeutic strategies for cancer treatment and radiopharmaceuticals using 47Sc.

Keywords

Acknowledgement

This works was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT(NRF-2017M2A2A6A05016598) and Korea Atomic Energy Research Institute (KAERI) Major Project (524440-22).

References

  1. Chao Y, Liang C, Yang Y, Wang G, Maiti D, Tian L, Wang F, Pan W, Wu S, Yang K, Liu.Z. Highly Effective Radioisotope Cancer Therapy with a Non-Therapeutic Isotope Delivered and Sensitized by Nanoscale Coordination Polymers. ACS Nano 2018;28:7519-28.
  2. Wotherspoon AT, Safavi-Naeini M, Banati RB. Radiopharmaceuticals for diagnosis in nuclear medicine: a short review. Ecletica Quimica 2019;44:11-9.
  3. Jackson SE, Chester JD. Personalised cancer medicine. Int. J Cancer 2015;137: 262-6. https://doi.org/10.1002/ijc.28940
  4. Arrieta O, Cardona AF, Bramuglia GF, Gallo A, Campos-Parra AD, Serrano S, Castro M, Aviles A, Amorin E, Kirchuk R, Cuello M, Borbolla J, Riemersma O, Becerra H, Rosell R, CLICaP. Genotyping non-small cell lung cancer (NSCLC) in Latin America. J Thorac Oncol 2011;6:1955-9. https://doi.org/10.1097/JTO.0b013e31822f655f
  5. Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, Gonzalez-Larriba JL, Paz-Ares L, Bover I, Garcia-Campelo R, Moreno MA, Catot S, Rolfo C, Reguart N, Palmero R, Sanchez JM, Bastus R, Mayo C, Bertran-Alamillo J, Molina MA, Sanchez JJ, Taron M, Spanish Lung Cancer Group. Screening for epidermal growth factor Receptor mutations in lung cancer. N Engl J Med 2009;361:958-67. https://doi.org/10.1056/NEJMoa0904554
  6. Siwowska K, Guzik P, Domnanich KA, Monne Rodriguez JM, Bernhardt P, Ponsard B, Hasler R, Borgna F, Schibli R, Koster U, Meulen NP, Muller C. Therapeutic potential of 47Sc in comparison to 177Lu and 90Y:preclinical investigations. Pharmaceutics 2019;20,11(8):424.
  7. Chakravarty R, Goel S, Valdovinos HF, Hernandez R, Hong H, Nickles RJ, Cai W. Matching the decay half-life with the biological half-life: Immuno-PET imaging with (44)Sc-labeled cetuximab fab fragment. Bioconjug Chem 2014;25:2197-204. https://doi.org/10.1021/bc500415x
  8. Honarvar H, Muller C, Cohrs S, Haller S, Westerlund K, Karlstrom AE, Meulen NP, Schibli R, Tolmachev V. Evaluation of the first (44)Sc-la-beled Affibody molecule for imaging of HER2-expressing tumors. Nucl Med Biol 2017;45:15-21. https://doi.org/10.1016/j.nucmedbio.2016.10.004
  9. Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol 2018;12:3-20. https://doi.org/10.1002/1878-0261.12155
  10. Shi Y, Siu-Kie Au J, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, Heeroma K, Itoh Y, Cornelio G, Yang PC. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non--small-cell lung cancer of adenocarcinoma histology. J Thorac Oncol 2014;9:154-62. https://doi.org/10.1097/JTO.0000000000000033
  11. Camp ER, Summy J, Bauer TW, Liu W, Gallick GE, Lee ME. Molecular mechanism of resistance to therapies targeting the epidermal growth Factor receptor. Clin Cancer Res 2005;11:397-405. https://doi.org/10.1158/1078-0432.397.11.1
  12. Harding J, Burtness B. Cetuximab: an epidermal growth factor receptor chimeric human-murine monoclonal antibody. Drugs Today 2005;41:107-27. https://doi.org/10.1358/dot.2005.41.2.882662
  13. Chidharla A, Paris M, Kasi A. Cetuximab. Stat Pearls 2021.
  14. Domnanich KA, Muller C, Benesova M, Dressler R, Haller S, Koster U, Ponsard B, Schibli R, Turler A, Meulen NP. 47Sc as useful β--emitter for the radiotheragnostic paradigm: A comparative study of feasible production routes. EJNMMI Radiopharm Chem 2017;2:5. https://doi.org/10.1186/s41181-017-0024-x
  15. Millier C, Domnanich KA, Umbricht CA, Meulen NP. Scandium and terbium radionuclides for radiotheranostics: Current state of development towards clinical application. BrJRadiol2018;91(1091):20180074.
  16. KumarN, R Singh DNB RK, Dutta D, Kheruka SC. 177Lu a noble tracer: Future ofpersonalized radionuclide therapy. Clin Oncol2017;2: 1249.
  17. Goldstein NI, Prewett M, Zuklys K, Rockwell P, Mendelsohn J. Biological efficacy of a chimeric antibody to the epidermal grow factor receptor in a human tumor xenograft model. Clin Cancer Res 1995;1: 1311-18.
  18. Sunada H, Magun BE, Mendelsohn J, Macleod CL. Monoclonal-antibody against epidermal growth-factor receptor is internalized without stimulating receptor phosphorylation. Proc Natl Acad Sci USA 1986;83:3825-29. https://doi.org/10.1073/pnas.83.11.3825
  19. Wong SF. Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Clin Ther 2005;27:684-94. https://doi.org/10.1016/j.clinthera.2005.06.003
  20. Chen LY, Molina-Vila MA, Ruan SY, Su KY, Liao WY, Yu KL, Ho CC, Shih JY, Yu CJ, Yang JCH, Rosell R, Yang PC. Coexistence of EGFR T790M mutation and common activating mutations in pretreatment non-small cell lung cancer: A systematic review and meta-analysis. Lung Cancer2016;94:46-53.
  21. Mogi A, Kuwano H. TP53 mutations in non small cell lung cancer. J Biomed Biotechnol 2011;583929.
  22. Vaughan CA, Pearsall I, Singh S, Windle B, Deb SP, Grossman SR, Yeudall WA, Deb S. Addiction of lung cancer cells to GOF p53 is promoted by upregulation of EGFR through multiple contacts with p53 transactivation domain. Oncotarget 2016;15:12426-46.
  23. Lee JM, Bernstein A. P53 mutations increase resistance to ionizing radiation. Proc Natl Acad Sci USA 1993;90:5742-46. https://doi.org/10.1073/pnas.90.12.5742