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Radioisotopic Localization of 90Yttrium–Ibritumomab Tiuxetan in Patients with CD20+ Non-Hodgkin’s Lymphoma

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Abstract

Purpose

90Yttrium-ibritumomab-tiuxetan (Zevalin) is an effective treatment for relapsed or refractory low-grade, follicular, or transformed B-cell NHL. The purpose of this study is to assess whether tissue and cellular localization of 90Y-ibritumomab–tiuxetan determined by autoradiography and radioactivity localized to tumor tissue might enhance our understanding of the mechanism of action of radioimmunotherapy.

Methods

Eight eligible patients had CD20+ NHL, a bulky peripheral lymph node, and were scheduled for 90Y-ibritumomab–tiuxetan treatment. 2-Deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) was performed prior to treatment and at 12 weeks after therapy for assessment of response. Bone marrow, lymph node, and blood samples were collected 114 ± 3 h after 14.8 MBq/kg 90Y-ibritumomab-tiuxetan and processed for histology, scintillation counting, and microscopic autoradiography.

Results

Pericellular membrane localization of 90Y-ibritumomab–tiuxetan to lymphoma cells was observed by autoradiography in the involved areas of lymph node with absence of significant localization in histologically normal sections of bone marrow. Pericellular radioactivity and the highest quantitative radioactivity were observed in lymph node samples of responding patients.

Conclusions

90Y-ibritumomab-tiuxetan localizes to the surface membrane of CD20+ lymphoma cells in affected lymph nodes. The patients with the highest quantitative concentration of radioactivity to the lymph node as determined by scintillation counting were observed to have a clinical and FDG-PET/CT response.

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References

  1. Anderson KC, Bates MP, Slaughenhoupt BL et al (1984) Expression of human B cell-associated antigen on leukemias and lymphomas: a model of human B cell differentiation. Blood 63:1424–1433

    CAS  PubMed  Google Scholar 

  2. Cartron G, Watier H, Golay J et al (2004) From the bench to the bedside: ways to improve rituximab efficacy. Blood 104(9):2635–2642

    Article  CAS  PubMed  Google Scholar 

  3. Bubien JK, Zhou LJ, Bell PD et al (1993) Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes. J Cell Biol 121:1121–1132

    Article  CAS  PubMed  Google Scholar 

  4. Tedder TF, Engel P (1994) CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today 15(9):450–454, Sep

    Article  CAS  PubMed  Google Scholar 

  5. Flieger D, Renoth S, Beier I et al (2000) Mechanism of cytotoxicity induced by chimeric mouse human monoclonal antibody IDEC-C2B8 in CD20-expressing lymphoma cell lines. Cell Immunol 204:55–63

    Article  CAS  PubMed  Google Scholar 

  6. Golay J, Zaffaroni L, Vaccari T et al (2000) Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood 95:3900–3908

    CAS  PubMed  Google Scholar 

  7. Reff ME, Carmer K, Chambers KS et al (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445

    CAS  PubMed  Google Scholar 

  8. Golay J, Lazzaari M, Facchinetti V et al (2001) CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59. Blood 98:3383–3389

    Article  CAS  PubMed  Google Scholar 

  9. Weng WK, Levy R (2001) Expression of complement inhibitors CD46, C55, and CD59 on tumor cells does not predict clinical outcome after rituximab treatment in follicular non-Hodgkin lymphoma. Blood 98:1352–1357

    Article  CAS  PubMed  Google Scholar 

  10. Manches O, Lui G, Chaperot L, Gressin R et al (2003) In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood 101(3):949–954

    Article  CAS  PubMed  Google Scholar 

  11. Jazireha AR, Vega MI, Bonavida B (2007) Development of rituximab-resistant lymphoma clones with altered cell signalling and cross-resistance to chemotherapy. Cancer Res 67(3):1270–1281, Feb 1

    Article  Google Scholar 

  12. Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ Vose JM (2001) Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin’s lymphomas. J Clin Oncol 19(19):3929–3937

    Google Scholar 

  13. Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D, Goris M (2005) Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol 23(4):712–719

    Article  CAS  PubMed  Google Scholar 

  14. Witzig TE, White CA, Wiseman GA et al (1999) Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin’s lymphoma. J Clin Oncol 17:3793–3803

    CAS  PubMed  Google Scholar 

  15. Witzig TE, Flinn IW, Gordon LI et al (2002) Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol 20:3262–3269

    Article  CAS  PubMed  Google Scholar 

  16. Witzig TE, Gordon LI, Cabanillas F et al (2002) Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol 20:2453–2463

    Article  CAS  PubMed  Google Scholar 

  17. Witzig TE, White CA, Gordon LI et al (2003) Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-Hodgkin's lymphoma. J Clin Oncol 21:1263–1270

    Article  CAS  PubMed  Google Scholar 

  18. Zelenetz AD (1999) Radioimmunotherapy for lymphoma. Curr Opin Oncol 11:375–380

    Article  CAS  PubMed  Google Scholar 

  19. DeNardo GL (2005) Comcepts in radioimmunotherapy and immunotherapy: radioimmunotherapy from a Lym-1 perspective. Semin Oncol 32(1):S27–S35

    Article  CAS  PubMed  Google Scholar 

  20. Juweid M, Newman RA, Chaing P et al (1992) Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier. Cancer Res 52:5144–5153

    CAS  PubMed  Google Scholar 

  21. Juweid M (2002) Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma: from clinical trials to clinical practice. J Nuc Med 43(11):1507–1529

    CAS  Google Scholar 

  22. Press OW (1999) Radiolabeled antibody therapy of B-cell lymphomas. Semin Oncol 26(suppl 14):58–65

    CAS  PubMed  Google Scholar 

  23. Wiseman GA, Gordon LI, Multani PS et al (2002) Ibritumomab tiuxetan radioimmunotherpay for patients with relapsed or refracroty non-Hodgkin’s lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood 99:4336–4342

    Article  CAS  PubMed  Google Scholar 

  24. Gordon LI, Molina A, Witzig T et al (2004) Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase 1–2 study. Blood 103:4429–4431

    Article  CAS  PubMed  Google Scholar 

  25. Gregory SA, Leonard JP, Vose JM et al (2005) Superior outcomes associated with earlier use: experience with tositumomab and Iodine I 131 tositumomab in 1,177 patients (pts) with low-grade, follicular, and transformed non-Hodgkin’s lymphoma NHL). J Clin Oncol 2005 ASCO Annual Meeting Proceedings 23[16S]

  26. Witzig TE, Gordon LL, Cabanillas F (2002) Randomized controlled trial of yttrium-90 labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol 20:2453–2463

    Article  CAS  PubMed  Google Scholar 

  27. Witzig TE, Flinn IW, Gordon LI et al (2002) Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol 20(15):3262–3269

    Article  CAS  PubMed  Google Scholar 

  28. Wiseman GA, Witzig TE (2005) Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) induces long-term durable responses in patients with relapsed or refractory B-Cell non-Hodgkin’s lymphoma. Cancer Biother Radiopharm 20:185–188

    Article  CAS  PubMed  Google Scholar 

  29. Coleman M, Kaminski MS, Knox SJ et al (2003) The BEXXARÒ therapeutic regimen (tositumomab and iodine I 131 tositumomab) produced durable complete remissions in heavily pretreated patients with non-Hodgkin’s lymphoma (NHL), rituximab/refractory disease, and rituximab-naïve disease. Blood 102. Abstract 89

  30. Kashyap A, Zelenetz A, Vose J et al (2003) Tositumomab and iodine I 131 tositumomab produces a meaningful therapeutic benefit for patients with relapsed, refractory, and transformed low-grade (LG) NHL: summary of the long-term response population (LTRP). Proc Am Soc Clin Oncol 22:576. Abstract 2316

    Google Scholar 

  31. Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M (2005) Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin’s lymphomas. J Clin Oncol 23(30):7565–7573

    Article  CAS  PubMed  Google Scholar 

  32. Davis TA, Czerwinski DK, Levy R (1999) Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression. Clin Cancer Res 5:611–615

    CAS  PubMed  Google Scholar 

  33. Grillo-Lopez A, Kunkel L (2000) Correspondence re: therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression. Clin Cancer Res 6:317–318

    CAS  PubMed  Google Scholar 

  34. Cheson BD, Horning SJ, Coiffier B et al (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s Lymphomas. J Clin Oncol 17:1244–1253

    CAS  PubMed  Google Scholar 

  35. Juweid ME, Wiseman GA, Vose JM et al (2005) Response assessment of aggresssive non-Hodgkin’s lymphoma by integrated international workshop criteria and fluorine-18-flurodeoxyglucose positron emission tomography. J Clin Oncol 23:4652–4661

    Article  PubMed  Google Scholar 

  36. Jerusalem G, Beguin Y, Fassotte MF et al (1999) Whole-body positron emission tomography using 18 F-fluorodeoxyglucose for posttrestemnt evaluation in Hodgkin’s disease and non-Hodgkin’s lymphoma has a higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 94:429–433

    CAS  PubMed  Google Scholar 

  37. Spaepen K, Stroobants S, Dupont P et al (2001) Prognostic value of positron emission tomography (PET) with fluorine 18 fluorodeoxyglucose ([18F]Fdg) after first-line chemotherapy in non-Hodgkin’s lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol 19(2):414–419

    CAS  PubMed  Google Scholar 

  38. Binder M, Otto F, Mertelsmann R et al (2006) The epitope recognized by rituximab. Blood 108:1975–1978

    Article  CAS  PubMed  Google Scholar 

  39. Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987–998

    Article  CAS  PubMed  Google Scholar 

  40. Kaufmann H, Rafiq K, Woehrer S et al (2004) Brief report: antiumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. Blood 104:2269–2271

    Article  CAS  PubMed  Google Scholar 

  41. Skvortsova I, Popper B, Skvortsov S et al (2005) Pretreatment with rituximab enhances radiosensitivity of non-Hodgkin’s lymphoma cells. J Radiat Res 46241–248

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Acknowledgement

This research was funded by a grant from BiogenIdec Pharmaceuticals.

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Correspondence to S. A. Jacobs.

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Jacobs, S.A., Harrison, A.M., Swerdlow, S.H. et al. Radioisotopic Localization of 90Yttrium–Ibritumomab Tiuxetan in Patients with CD20+ Non-Hodgkin’s Lymphoma. Mol Imaging Biol 11, 39–45 (2009). https://doi.org/10.1007/s11307-008-0170-3

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