Nuclear Medicine and Biology
Volume 39, Issue 1 , Pages 3-13 , January 2012

Preparation and preclinical evaluation of 177Lu-nimotuzumab targeting epidermal growth factor receptor overexpressing tumors

Received 6 April 2011 ,Revised 30 June 2011 ,Accepted 3 July 2011.

References 

  1. Schaefer NG, Ma J, Huang P, Buchanan J, Wahl RL. Radioimmunotherapy in non-Hodgkin lymphoma: opinions of U.S. medical oncologists and hematologists. J Nucl Med. 2010;51(6):987–994
  2. Sharkey RM, Goldenberg DM. Perspectives on cancer therapy with radiolabeled monoclonal antibodies. J Nucl Med. 2005;46(Suppl 1):115S–127S
  3. Govindan SVG, David M. Immunoconjugate anticancer therapeutics. Discovery. 2010;371–392
  4. Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol. 2006;33(4):369–385
  5. Rocha-Lima CM, Soares HP, Raez LE, Singal R. EGFR targeting of solid tumors. Cancer Control. 2007;14(3):295–304
  6. Carpenter G, Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216
  7. Real FX, Rettig WJ, Chesa PG, Melamed MR, Old LJ, Mendelsohn J. Expression of epidermal growth factor receptor in human cultured cells and tissues: relationship to cell lineage and stage of differentiation. Cancer Res. 1986;46(9):4726–4731
  8. Herbst RS, Langer CJ. Epidermal growth factor receptors as a target for cancer treatment: the emerging role of IMC-C225 in the treatment of lung and head and neck cancers. Semin Oncol. 2002;29(1 Suppl 4):27–36
  9. Talavera A, Friemann R, Gomez-Puerta S, Martinez-Fleites C, Garrido G, Rabasa A, et al. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res. 2009;69(14):5851–5859
  10. Martinelli E, De Palma R, Orditura M, De Vita F, Ciardiello F. Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin Exp Immunol. 2009;158(1):1–9
  11. Mateo C, Moreno E, Amour K, Lombardero J, Harris W, Perez R. Humanization of a mouse monoclonal antibody that blocks the epidermal growth factor receptor: recovery of antagonistic activity. Immunotechnology. 1997;3(1):71–81
  12. Vallis KA, Reilly RM, Chen P, Oza A, Hendler A, Cameron R, et al. A phase I study of 99mTc-hR3 (DiaCIM), a humanized immunoconjugate directed towards the epidermal growth factor receptor. Nucl Med Commun. 2002;23(12):1155–1164
  13. Allan DG. Nimotuzumab: evidence of clinical benefit without rash. Oncologist. 2005;10(9):760–761
  14. Spicer J. Technology evaluation: nimotuzumab, the Center of Molecular Immunology/YM BioSciences/Oncoscience. Curr Opin Mol Ther. 2005;7(2):182–191
  15. Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007;29(7):467–509
  16. Casaco A, Lopez G, Garcia I, Rodriguez JA, Fernandez R, Figueredo J, et al. Phase I single-dose study of intracavitary-administered nimotuzumab labeled with 188Re in adult recurrent high-grade glioma. Cancer Biol Ther. 2008;7(3):333–339
  17. Brouwers AH, van Eerd JE, Frielink C, Oosterwijk E, Oyen WJ, Corstens FH, et al. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re. J Nucl Med. 2004;45(2):327–337
  18. Ehrhardt GJ, Ketring AR, Ayers LM. Reactor-produced radionuclides at the University of Missouri Research Reactor. Appl Radiat Isot. 1998;49(4):295–297
  19. Mausner LF, Srivastava SC. Selection of radionuclides for radioimmunotherapy. Med Phys. 1993;20(2 Pt 2):503–509
  20. Liu S. Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides. Adv Drug Deliv Rev. 2008;60(12):1347–1370
  21. Liu S, Edwards DS. Bifunctional chelators for therapeutic lanthanide radiopharmaceuticals. Bioconjug Chem. 2001;12(1):7–34
  22. Meares CF, McCall MJ, Reardan DT, Goodwin DA, Diamanti CI, McTigue M. Conjugation of antibodies with bifunctional chelating agents: isothiocyanate and bromoacetamide reagents, methods of analysis, and subsequent addition of metal ions. Anal Biochem. 1984;142(1):68–78
  23. Konishi S, Hamacher K, Vallabhajosula S, Kothari P, Bastidas D, Bander N, et al. Determination of immunoreactive fraction of radiolabeled monoclonal antibodies: what is an appropriate method?. Cancer Biother Radiopharm. 2004;19(6):706–715
  24. Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46(6):1023–1027
  25. Kirschner AIR, Beierwalters W. Radiation dosimetry of 131I-19-iodocholesterol: the pitfalls of using tissue concentration data, the author's reply. J Nucl Med. 1975;16:248–249
  26. Delbeke D. Reaching out with radioimmunotherapy. J Nucl Med. 2010;51(11):16N
  27. Boswell CA, Brechbiel MW. Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view. Nucl Med Biol. 2007;34(7):757–778
  28. Ramakrishnan MS, Eswaraiah A, Crombet T, Piedra P, Saurez G, Iyer H, et al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. MAbs. 2009;1(1):41–48
  29. Greta Garrido AR, Elias Gracia, Ilia Tikhomirov and Rolando Perez. Binding properties of the anti-EGFR monoclonal antibody, nimotuzumab, limit interaction with the EGFR in renal and epidermal cells. 100th AACR Annual Meeting; Apr 18-22. Denver, CO: In: Proc Am Assoc Cancer Res; 2009. p. Abstract nr 2763.
  30. Beckford DR, Xiques CA, Leyva MR, Pérez MM, Casanova EG, Zamora BM. New radioimmunoconjugate 90Y-DOTA-h-R3. Synthesis and radiolabeling. Nucleus. 2007;41:3–8
  31. Castillo AX, Olive KI, Gonzalez EC, Beckford D, Montaña RL, Alvarez AM, et al. An adapted purification procedure to improve the quality of 90Y for clinical use. Radiochim Acta. 2009;97(97):739–746
  32. Milenic DE, Garmestani K, Chappell LL, Dadachova E, Yordanov A, Ma D, et al. In vivo comparison of macrocyclic and acyclic ligands for radiolabeling of monoclonal antibodies with 177Lu for radioimmunotherapeutic applications. Nucl Med Biol. 2002;29(4):431–442
  33. Rasaneh S, Rajabi H, Babaei MH, Daha FJ. 177Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer. Nucl Med Biol. 2010;37(8):949–955
  34. Mohsin H, Fitzsimmons J, Shelton T, Hoffman TJ, Cutler CS, Lewis MR, et al. Preparation and biological evaluation of 111In-, 177Lu- and 90Y-labeled DOTA analogues conjugated to B72.3. Nucl Med Biol. 2007;34(5):493–502
  35. Almqvist Y, Steffen AC, Tolmachev V, Divgi CR, Sundin A. In vitro and in vivo characterization of 177Lu-huA33: a radioimmunoconjugate against colorectal cancer. Nucl Med Biol. 2006;33(8):991–998
  36. Zacchetti A, Coliva A, Luison E, Seregni E, Bombardieri E, Giussani A, et al. (177)Lu- labeled MOv18 as compared to (131)I- or (90)Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts. Nucl Med Biol. 2009;36(7):759–770
  37. Morales-Morales A, Duconge J, Caballero-Torres I, Nunez-Gandolff G, Fernandez E, Iznaga-Escobar N. Biodistribution of 99mTc-labeled anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody h-R3 in a xenograft model of human lung adenocarcinoma. Nucl Med Biol. 1999;26(3):275–279
  38. Tabrizi M, Tseng C, Roskos L. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006;11(1-2):81–88
  39. Knogler K, Grunberg J, Novak-Hofer I, Zimmermann K, Schubiger PA. Evaluation of 177Lu-DOTA-labeled aglycosylated monoclonal anti-L1-CAM antibody chCE7: influence of the number of chelators on the in vitro and in vivo properties. Nucl Med Biol. 2006;33(7):883–889
  40. Pnwar P, Iznaga-Escobar N, Mishra P, Srivastava V, Sharma RK, Chandra R, et al. Radiolabeling and biological evaluation of DOTA-Ph-Al derivative conjugated to anti-EGFR antibody ior egf/r3 for targeted tumor imaging and therapy. Cancer Biol Ther. 2005;4(8):854–860
  41. Griffiths GL, Govindan SV, Sharkey RM, Fisher DR, Goldenberg DM. 90Y-DOTA-hLL2: an agent for radioimmunotherapy of non-Hodgkin's lymphoma. J Nucl Med. 2003;44(1):77–84
  42. Morales AA, Duconge J, Alvarez-Ruiz D, Becquer-Viart ML, Nunez-Gandolff G, Fernandez E, et al. Humanized versus murine anti-human epidermal growth factor receptor monoclonal antibodies for immunoscintigraphic studies. Nucl Med Biol. 2000;27(2):199–206
  43. Reilly RM, Kiarash R, Sandhu J, Lee YW, Cameron RG, Hendler A, et al. A comparison of EGF and MAb 528 labeled with 111In for imaging human breast cancer. J Nucl Med. 2000;41(5):903–911
  44. Wen X, Wu QP, Ke S, Ellis L, Charnsangavej C, Delpassand AS, et al. Conjugation with (111)In-DTPA-poly(ethylene glycol) improves imaging of anti-EGF receptor antibody C225. J Nucl Med. 2001;42(10):1530–1537
  45. Liu Z, Liu Y, Jia B, Zhao H, Jin X, Li F, et al. Epidermal growth factor receptor-targeted radioimmunotherapy of human head and neck cancer xenografts using 90Y-labeled fully human antibody panitumumab. Mol Cancer Ther. 2010;9(8):2297–2308
  46. Coliva A, Zacchetti A, Luison E, Tomassetti A, Bongarzone I, Seregni E, et al. 90Y Labeling of monoclonal antibody MOv18 and preclinical validation for radioimmunotherapy of human ovarian carcinomas. Cancer Immunol Immunother. 2005;54(12):1200–1213
  47. Iznaga Escobar N, Morales AM, Duconge J, Torres IC, Fernandez E, Gomez JA. Pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats. Nucl Med Biol. 1998;25(1):17–23
  48. Torres LA, Coca MA, Batista JF, Casaco A, Lopez G, Garcia I, et al. Biodistribution and internal dosimetry of the 188Re-labelled humanized monoclonal antibody anti-epidemal growth factor receptor, nimotuzumab, in the locoregional treatment of malignant gliomas. Nucl Med Commun. 2008;29(1):66–75
  49. Zuckier LS, Berkowitz EZ, Sattenberg RJ, Zhao QH, Deng HF, Scharff MD. Influence of affinity and antigen density on antibody localization in a modifiable tumor targeting model. Cancer Res. 2000;60(24):7008–7013
  50. Boland WK, Bebb G. Nimotuzumab: a novel anti-EGFR monoclonal antibody that retains anti-EGFR activity while minimizing skin toxicity. Expert Opin Biol Ther. 2009;9(9):1199–1206
  51. Garrido G, Tikhomirov IA, Rabasa A, Yang E, Gracia E, Iznaga N, et al. Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile. Cancer Biol Ther. 2011;11(4):373–382

 This research was supported by EUREKA Grant No. E08018 and Project NPVII 2B06165 from the Czech Ministry of Education, Youth and Sports.

☆☆ Conflicts of interest statement: The authors declare that they have no conflicts of interest.

PII: S0969-8051(11)00154-5

doi: 10.1016/j.nucmedbio.2011.07.001

Nuclear Medicine and Biology
Volume 39, Issue 1 , Pages 3-13 , January 2012